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[PMID]:29309791
[Au] Autor:Gundala NKV; Naidu VGM; Das UN
[Ad] Endereço:BioScience Research Centre, Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India.
[Ti] Título:Amelioration of streptozotocin-induced type 2 diabetes mellitus in Wistar rats by arachidonic acid.
[So] Source:Biochem Biophys Res Commun;496(1):105-113, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Traditionally arachidonic acid (AA, 20:4 n-6) is considered as a pro-inflammatory molecule since it forms precursor to prostaglandins (PGs), leukotrienes (LTs) and thromboxanes (TXs) that have pro-inflammatory actions. Type 2 diabetes mellitus (type 2 DM) is considered as a low-grade systemic inflammatory condition in which circulating PGs and LTs are increased. Streptozotocin (STZ)-induced type 2 DM is used as a model of human type 2 DM in which peripheral insulin resistance, increased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and hyperglycemia occurs. In the present study, we observed that oral supplementation of AA prevented STZ-induced type 2 DM in Wistar rats by restoring hyperglycemia, plasma levels of TNF-α and IL-6; adipose tissue NF-kB and lipocalin 2 (LPCLN2) and pancreatic tissue NF-kB and 5- and 12- lipoxygenase enzymes to normal. AA treatment enhanced insulin sensitivity and plasma lipoxin A4 (LXA4) levels, a potent anti-inflammatory molecule derived from AA. These results are supported by our previous studies wherein it was noted that plasma phospholipid content of AA and circulating LXA4 levels are low in those with type 2 DM. In a preliminary study, we also noted that high-fat-diet (HFD)-induced type 2 DM in Wistar rats can be prevented by oral supplementation of AA. These results suggest AA has anti-inflammatory and anti-diabetic actions by enhancing the production of its anti-inflammatory metabolite LXA4.
[Mh] Termos MeSH primário: Ácido Araquidônico/administração & dosagem
Citocinas/imunologia
Diabetes Mellitus Tipo 2/tratamento farmacológico
Diabetes Mellitus Tipo 2/imunologia
Mediadores da Inflamação/imunologia
Lipoxinas/imunologia
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios/administração & dosagem
Diabetes Mellitus Tipo 2/induzido quimicamente
Relação Dose-Resposta a Droga
Hipoglicemiantes/administração & dosagem
Masculino
Ratos
Ratos Wistar
Estreptozocina
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Cytokines); 0 (Hypoglycemic Agents); 0 (Inflammation Mediators); 0 (Lipoxins); 0 (lipoxin A4); 27YG812J1I (Arachidonic Acid); 5W494URQ81 (Streptozocin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  2 / 892 MEDLINE  
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[PMID]:28753648
[Au] Autor:Reis MB; Pereira PAT; Caetano GF; Leite MN; Galvão AF; Paula-Silva FWG; Frade MAC; Faccioli LH
[Ad] Endereço:Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
[Ti] Título:Lipoxin A4 encapsulated in PLGA microparticles accelerates wound healing of skin ulcers.
[So] Source:PLoS One;12(7):e0182381, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lipoxin A4 (LXA4) is involved in the resolution of inflammation and wound healing; however, it is extremely unstable. Thus, to preserve its biological activities and confer stability, we encapsulated LXA4 in poly-lactic-co-glycolic acid (PLGA) microparticles (LXA4-MS) and assessed its application in treating dorsal rat skin lesions. Ulcers were sealed with fibrin adhesive and treated with either LXA4-MS, unloaded microparticles (Un-MS), soluble LXA4, or PBS/glue (vehicle). All groups were compared at 0, 2, 7, and 14 days post-lesions. Our results revealed that LXA4-MS accelerated wound healing from day 7 and reduced initial ulcer diameters by 80%. Soluble LXA4, Un-MS, or PBS closed wounds by 60%, 45%, and 39%, respectively. LXA4-MS reduced IL-1ß and TNF-α, but increased TGF-ß, collagen deposition, and the number of blood vessels. Compared to other treatments, LXA4-MS reduced inflammatory cell numbers, myeloperoxidase (MPO) concentration, and metalloproteinase-8 (MMP8) mRNA in scar tissue, indicating decreased neutrophil chemotaxis. In addition, LXA4-MS treatment increased macrophages and IL-4, suggesting a positive impact on wound healing. Finally, we demonstrated that WRW4, a selective LXA4 receptor (ALX) antagonist, reversed healing by 50%, indicating that LXA4 must interact with ALX to induce wound healing. Our results show that LXA4-MS could be used as a pharmaceutical formulation for the treatment of skin ulcers.
[Mh] Termos MeSH primário: Ácido Láctico/química
Lipoxinas/química
Lipoxinas/uso terapêutico
Ácido Poliglicólico/química
Úlcera Cutânea/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Citocinas/metabolismo
Interleucina-1beta/metabolismo
Interleucina-6/metabolismo
Lipoxinas/farmacologia
Masculino
Neutrófilos/efeitos dos fármacos
Neutrófilos/metabolismo
Ratos
Ratos Wistar
Fator de Crescimento Transformador beta/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
Fator A de Crescimento do Endotélio Vascular/metabolismo
Cicatrização/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (Lipoxins); 0 (Transforming Growth Factor beta); 0 (Tumor Necrosis Factor-alpha); 0 (Vascular Endothelial Growth Factor A); 0 (lipoxin A4); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182381


  3 / 892 MEDLINE  
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[PMID]:28594958
[Au] Autor:Yang Y; Wang Y; Kong Y; Zhang X; Bai L
[Ad] Endereço:Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, ShenYang, Liaoning, China.
[Ti] Título:The effects of different frequency treadmill exercise on lipoxin A4 and articular cartilage degeneration in an experimental model of monosodium iodoacetate-induced osteoarthritis in rats.
[So] Source:PLoS One;12(6):e0179162, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim was to investigate the effects of different frequencies treadmill exercise with total exercise time being constancy on articular cartilage, lipoxin A4 (LXA4) and the NF-κB pathway in rat model of monosodium iodoacetate-induced osteoarthritis (OA). Fifty male Sprague-Dawley rats were randomly divided into five groups (n = 10): controls (CG), knee OA model (OAG), OA + treadmill exercise once daily (OAE1), OA + treadmill exercise twice daily, rest interval between exercise>4h (OAE2) and OA + treadmill exercise three times daily, rest interval between exercise>4h (OAE3). Rats were evaluated after completing the treadmill exercise program (speed, 18 m/min; total exercise time 60 min/day; 5 days/week for 8 weeks). Interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and LXA4 in serum and intra-articular lavage fluid were measured by ELISA. Changes in articular cartilage were evaluated by histology, immunohistochemistry, western blotting and quantitative real-time-PCR. LXA4 in the serum and intra-articular lavage fluid increased in all OAE groups, and histological evaluation indicated that the OAE3 group had the best treatment response. The expression of COL2A1 and IκB-ß in articular cartilage increased in all OAE groups vs the OAG group, whereas expression of IL-1ß, TNF-α, matrix metalloproteinase (MMP)-13, and NF-κB p65 was reduced in all OAE groups compared with the OAG. Under the condition of 60 min treadmill exercise with moderate-intensity, to fulfill in three times would have better chondroprotective effects than to fulfill in two or one time on monosodium iodoacetate-induced OA in rats. And it may be worked through the anti-inflammatory activity of LXA4 and the NF-κB pathway.
[Mh] Termos MeSH primário: Cartilagem Articular/metabolismo
Cartilagem Articular/patologia
Lipoxinas/metabolismo
Osteoartrite/induzido quimicamente
Osteoartrite/patologia
Condicionamento Físico Animal
[Mh] Termos MeSH secundário: Animais
Western Blotting
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Imuno-Histoquímica
Iodoacetatos
Articulações/patologia
Masculino
NF-kappa B/metabolismo
Osteoartrite/sangue
Reação em Cadeia da Polimerase
Ratos Sprague-Dawley
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Iodoacetates); 0 (Lipoxins); 0 (NF-kappa B); 0 (lipoxin A4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179162


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[PMID]:28522438
[Au] Autor:Ke Y; Zebda N; Oskolkova O; Afonyushkin T; Berdyshev E; Tian Y; Meng F; Sarich N; Bochkov VN; Wang JM; Birukova AA; Birukov KG
[Ad] Endereço:From the Department of Medicine, Lung Injury Center, Section of Pulmonary and Critical Medicine, University of Chicago, IL (Y.K., N.Z., O.O., T.A., Y.T., F.M., N.S., A.A.B., K.G.B.); National Jewish Health, Denver, CO (E.B.); National Cancer Institute at Frederick, MD (J.M.W.); and Institute of Phar
[Ti] Título:Anti-Inflammatory Effects of OxPAPC Involve Endothelial Cell-Mediated Generation of LXA4.
[So] Source:Circ Res;121(3):244-257, 2017 Jul 21.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) generates a group of bioactive oxidized phospholipid products with a broad range of biological activities. Barrier-enhancing and anti-inflammatory effects of OxPAPC on pulmonary endothelial cells are critical for prevention of acute lung injury caused by bacterial pathogens or excessive mechanical ventilation. Anti-inflammatory properties of OxPAPC are associated with its antagonistic effects on Toll-like receptors and suppression of RhoA GTPase signaling. OBJECTIVE: Because OxPAPC exhibits long-lasting anti-inflammatory and lung-protective effects even after single administration in vivo, we tested the hypothesis that these effects may be mediated by additional mechanisms, such as OxPAPC-dependent production of anti-inflammatory and proresolving lipid mediator, lipoxin A4 (LXA4). METHODS AND RESULTS: Mass spectrometry and ELISA assays detected significant accumulation of LXA4 in the lungs of OxPAPC-treated mice and in conditioned medium of OxPAPC-exposed pulmonary endothelial cells. Administration of LXA4 reproduced anti-inflammatory effect of OxPAPC against tumor necrosis factor-α in vitro and in the animal model of lipopolysaccharide-induced lung injury. The potent barrier-protective and anti-inflammatory effects of OxPAPC against tumor necrosis factor-α and lipopolysaccharide challenge were suppressed in human pulmonary endothelial cells with small interfering RNA-induced knockdown of LXA4 formyl peptide receptor-2 (FPR2/ALX) and in mFPR2 (mouse formyl peptide receptor 2) mice lacking the mouse homolog of human FPR2/ALX. CONCLUSIONS: This is the first demonstration that inflammation- and injury-associated phospholipid oxidation triggers production of anti-inflammatory and proresolution molecules, such as LXA4. This lipid mediator switch represents a novel mechanism of OxPAPC-assisted recovery of inflamed lung endothelium.
[Mh] Termos MeSH primário: Lesão Pulmonar Aguda/metabolismo
Anti-Inflamatórios não Esteroides/uso terapêutico
Células Endoteliais/efeitos dos fármacos
Células Endoteliais/metabolismo
Lipoxinas/metabolismo
Fosfatidilcolinas/uso terapêutico
[Mh] Termos MeSH secundário: Lesão Pulmonar Aguda/prevenção & controle
Animais
Anti-Inflamatórios não Esteroides/farmacologia
Células Cultivadas
Seres Humanos
Lipoxinas/farmacologia
Lipoxinas/uso terapêutico
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fosfatidilcolinas/farmacologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Lipoxins); 0 (Phosphatidylcholines); 0 (lipoxin A4); 0 (oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.116.310308


  5 / 892 MEDLINE  
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[PMID]:28485793
[Au] Autor:Shi Y; Pan H; Zhang HZ; Zhao XY; Jin J; Wang HY
[Ad] Endereço:Department of Cardiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. haiyann1976@sohu.com.
[Ti] Título:Lipoxin A4 mitigates experimental autoimmune myocarditis by regulating inflammatory response, NF-κB and PI3K/Akt signaling pathway in mice.
[So] Source:Eur Rev Med Pharmacol Sci;21(8):1850-1859, 2017 Apr.
[Is] ISSN:2284-0729
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Myocarditis, an acute inflammation disease of the heart, is a potentially lethal disease and can lead to sudden death. This study aims to investigate the therapeutic effect of lipoxin A4 (LXA4) on experimental autoimmune myocarditis (EAM) and to explore the underlying mechanism. MATERIALS AND METHODS: EAM was induced in BALB/c mice by injection of porcine cardiac myosin and LAX4 at doses of 10 or 50 µg/kg was administrated from day 1 to 21. The severity of myocarditis was evaluated by detection of heart weight/body weight (HW/BW) ratio and histopathological examination of the heart. Cardiac function and heart structure were assessed by echocardiography. Serum levels of Th1 and Th2 cytokines were determined by ELISA. Protein expression was detected by Western blot analysis. RESULTS: The results demonstrated that LXA4 mitigated the severity of myocarditis by decreasing HW/BW ratio and reducing infiltration of inflammatory cells. Echocardiographic analysis indicated that cardiac function of LXA4-treated rats was significantly improved compared with non-treated group. LXA4 treatment significantly increased the levels of Th1 cytokines (TNF-α and IL-6) and decreased Th2 cytokines (IL-4 and IL-10). Furthermore, LXA4 administration effectively inhibited NF-κB nuclear translocation and deactivated PI3K/Akt pathway. CONCLUSIONS: LXA4 has a protective effect against EAM by reducing the inflammatory response and inhibiting NF-κB and PI3K/Akt signaling pathway.
[Mh] Termos MeSH primário: Doenças Autoimunes/tratamento farmacológico
Lipoxinas/farmacologia
Miocardite/tratamento farmacológico
NF-kappa B/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Doenças Autoimunes/metabolismo
Citocinas/sangue
Camundongos
Camundongos Endogâmicos BALB C
Miocardite/metabolismo
Fosfatidilinositol 3-Quinases
Proteínas Proto-Oncogênicas c-akt/metabolismo
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Lipoxins); 0 (NF-kappa B); 0 (lipoxin A4); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170510
[St] Status:MEDLINE


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[PMID]:28259922
[Au] Autor:Wu SH; Wang MJ; Lü J; Chen XQ
[Ad] Endereço:Department of Pediatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
[Ti] Título:Signal transduction involved in lipoxin A4­induced protection of tubular epithelial cells against hypoxia/reoxygenation injury.
[So] Source:Mol Med Rep;15(4):1682-1692, 2017 Apr.
[Is] ISSN:1791-3004
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Previous studies have reported that lipoxin A4 (LXA4) may exert a renoprotective effect on ischemia/reperfusion injury in various animal models. The underlying mechanism of LXA4­induced renoprotection during ischemia/reperfusion injury remains to be elucidated. The present study investigated LXA4­induced protection on renal tubular cells subjected to hypoxia/reoxygenation (H/R) injury, and determined the effects of peroxisome proliferator­activated receptor­Î³ (PPARγ) and heme oxygenase­1 (HO­1) on LXA4 treatment. HK­2 human tubular epithelial cells exposed to H/R injury were pretreated with LXA4, signal molecule inhibitors or the HO­1 inhibitor zinc protoporphyrin­IX, or were transfected with PPARγ small interfering RNA (siRNA) or nuclear factor E2­related factor 2 (Nrf2) siRNA. The protein and mRNA expression levels of PPARγ and HO­1 were analyzed using western blotting and reverse transcription­quantitative polymerase chain reaction. Binding activity of Nrf2 to the HO­1 E1 enhancer was determined using chromatin immunoprecipitation. Nrf2 binding to the HO­1 antioxidant responsive element (ARE) was assessed using electrophoretic mobility shift assay. Preincubation of cells with LXA4 exposed to H/R injury led to a decreased production of inducible nitrogen oxide synthase, malondialdehyde, γ­glutamyl transpeptidase, leucine aminopeptidase and N­acetyl­ß­glucosaminidase. In addition, LXA4 pretreatment increased cell viability, protein and mRNA expression levels of PPARγ and HO­1 and PPARγ and HO­1 promoter activity. SB20358 is a p38 mitogen­activated protein kinase (p38 MAPK) pathway inhibitor, which reduced LXA4­induced PPARγ expression levels. LXA4 treatment upregulated p38 MAPK activation, Nrf2 nuclear translocation and increased binding activity of Nrf2 to HO­1 ARE and E1 enhancer in cells exposed to H/R injury. Transfection of the cells with PPARγ siRNA reduced the LXA4­induced Nrf2 translocation. Transfection of the cells with PPARγ siRNA or Nrf2 siRNA also reduced the LXA4­induced increase in HO­1 expression. In conclusion, LXA4­induced protection of renal tubular cells against H/R injury was associated with the induction of PPARγ and HO­1, via activation of the p38 MAPK pathway, as well as Nrf2 nuclear translocation and binding to HO­1 ARE and E1 enhancer. Therefore, LXA4­induced renoprotection is associated with activation of the p38 MAPK/PPARγ/Nrf2­ARE/HO­1 pathway.
[Mh] Termos MeSH primário: Citoproteção/efeitos dos fármacos
Células Epiteliais/patologia
Túbulos Renais/patologia
Lipoxinas/farmacologia
Oxigênio/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Elementos de Resposta Antioxidante/genética
Hipóxia Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Heme Oxigenase-1/genética
Heme Oxigenase-1/metabolismo
Seres Humanos
Malondialdeído/metabolismo
Fator 2 Relacionado a NF-E2/metabolismo
Óxido Nítrico Sintase Tipo II/metabolismo
PPAR gama/metabolismo
Transporte Proteico/efeitos dos fármacos
Superóxido Dismutase/metabolismo
Transcrição Genética/efeitos dos fármacos
Regulação para Cima/efeitos dos fármacos
gama-Glutamiltransferase/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipoxins); 0 (NF-E2-Related Factor 2); 0 (PPAR gamma); 0 (lipoxin A4); 4Y8F71G49Q (Malondialdehyde); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.15.1.1 (Superoxide Dismutase); EC 2.3.2.2 (gamma-Glutamyltransferase); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); S88TT14065 (Oxygen)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170522
[Lr] Data última revisão:
170522
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170306
[St] Status:MEDLINE
[do] DOI:10.3892/mmr.2017.6195


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[PMID]:28245134
[Au] Autor:Lee S; Nakahira K; Dalli J; Siempos II; Norris PC; Colas RA; Moon JS; Shinohara M; Hisata S; Howrylak JA; Suh GY; Ryter SW; Serhan CN; Choi AMK
[Ad] Endereço:1 Division of Pulmonary and Critical Care Medicine and.
[Ti] Título:NLRP3 Inflammasome Deficiency Protects against Microbial Sepsis via Increased Lipoxin B Synthesis.
[So] Source:Am J Respir Crit Care Med;196(6):713-726, 2017 Sep 15.
[Is] ISSN:1535-4970
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a major public health concern with high mortality and morbidity. Although inflammatory responses triggered by infection are crucial for host defense against invading microbes, the excessive inflammation often causes tissue damage leading to organ dysfunction. Resolution of inflammation, an active immune process mediated by endogenous lipid mediators (LMs), is important to maintain host homeostasis. OBJECTIVES: We sought to determine the role of the nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome in polymicrobial sepsis and regulation of LM biosynthesis. METHODS: We performed cecal ligation and puncture (CLP) using mice lacking NLRP3 inflammasome-associated molecules to assess mortality. Inflammation was evaluated by using biologic fluids including plasma, bronchoalveolar, and peritoneal lavage fluid. Local acting LMs in peritoneal lavage fluid from polymicrobacterial septic mice were assessed by mass spectrometry-based metabololipidomics. MEASUREMENTS AND MAIN RESULTS: Genetic deficiency of NLRP3 inhibited inflammatory responses and enhanced survival of CLP-induced septic mice. NLRP3 deficiency reduced proinflammatory LMs and increased proresolving LM, lipoxin B (LXB ) in septic mice, and in macrophages stimulated with LPS and ATP. Activation of the NLRP3 inflammasome induced caspase-7 cleavage and pyroptosis. Caspase-7 deficiency similarly reduced inflammation and mortality in CLP-induced sepsis, and increased LXB production in vivo and in vitro. Exogenous application of LXB reduced inflammation, pyroptosis, and mortality of mice after CLP. CONCLUSIONS: Genetic deficiency of NLRP3 promoted resolution of inflammation in polymicrobial sepsis by relieving caspase-7-dependent repression of LXB biosynthesis, and increased survival potentially via LXB production and inhibition of proinflammatory cytokines.
[Mh] Termos MeSH primário: Proteínas de Transporte/genética
Proteínas de Transporte/metabolismo
Inflamassomos/genética
Inflamassomos/metabolismo
Lipoxinas/metabolismo
Sepse/imunologia
Sepse/microbiologia
[Mh] Termos MeSH secundário: Animais
Camundongos
Substâncias Protetoras
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Inflammasomes); 0 (Lipoxins); 0 (Protective Agents)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171015
[Lr] Data última revisão:
171015
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170301
[St] Status:MEDLINE
[do] DOI:10.1164/rccm.201604-0892OC


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[PMID]:28241993
[Au] Autor:Gundala NK; Naidu VG; Das UN
[Ad] Endereço:BioScience Research Centre, Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam, India.
[Ti] Título:Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo.
[So] Source:Nutrition;35:61-80, 2017 Mar.
[Is] ISSN:1873-1244
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The aim of this study was to observe whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5 F) cells against streptozotocin (STZ)-induced apoptosis in vitro and type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) in vivo and if so, what would be the mechanism of this action. METHODS: RIN5 F cells were used for the in vitro study, whereas the in vivo study was performed in Wistar rats. STZ was used to induce apoptosis of RIN5 F cells in vitro and T1- and T2DM in vivo. The effect of PUFAs: γ-linolenic acid (GLA), arachidonic acid (AA) of ω-6 series, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of ω-3 series; cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors and antiinflammatory metabolite of AA and DHA, lipoxin A4 (LXA4), and resolvin D2 and protectin, respectively against STZ-induced cytotoxicity to RIN5 F cells in vitro and LXA4 against T1- and T2DM in vivo was studied. Changes in the antioxidant content, lipid peroxides, nitric oxide, and expression of PDX1, P65, nuclear factor-κb (NF-κb), and IKB genes in STZ-treated RIN5 F cells in vitro and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue of T1- and T2DM and LPCLN2 (lipocalin 2), NF-κb, IKB I in adipose tissue of T2DM after LXA4 treatment were studied. Plasma glucose, insulin, and tumor necrosis factor (TNF)-α levels also were measured in STZ-induced T1- and T2DM Wistar rats. RESULTS: Among all PUFAs tested, AA and EPA are the most effective against STZ-induced cytotoxicity to RIN5 F cells in vitro. Neither COX nor LOX inhibitors blocked the cytoprotective action of AA in vitro and T1- and T2DM by STZ. LXA4 production by RIN5 F cells in vitro and plasma LXA4 levels in STZ-induced T1- and T2DM animals were decreased by STZ that reverted to normal after AA treatment. AA prevented both T1- and T2DM induced by STZ. Antiinflammatory metabolite of AA and LXA4 prevented both T1- and T2DM induced by STZ. The expression of Pdx1, NF-κb, IKB genes in the pancreas and plasma TNF-α levels in T1- and T2DM; Nrf2, Glut2, COX2, and iNOS proteins in pancreatic tissue of T1DM and LPCLN2, NF-κb, IKB I in adipose tissue of T2DM reverted to normal in LXA4-treated animals. CONCLUSION: Both AA and LXA4 prevented STZ-induced cytotoxicity to RIN5 F cells in vitro and T1- and T2DM in vivo, suggesting that these two bioactive lipids may function as antidiabetic molecules. AA is beneficial against STZ-induced cytotoxicity and T1- and T2DM by enhancing the production of LXA4.
[Mh] Termos MeSH primário: Ácido Araquidônico/farmacologia
Diabetes Mellitus Tipo 1/tratamento farmacológico
Diabetes Mellitus Tipo 2/tratamento farmacológico
Lipoxinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Glicemia/metabolismo
Linhagem Celular
Ciclo-Oxigenase 2/genética
Ciclo-Oxigenase 2/metabolismo
Diabetes Mellitus Experimental/induzido quimicamente
Diabetes Mellitus Experimental/tratamento farmacológico
Ácidos Docosa-Hexaenoicos/farmacologia
Ácido Eicosapentaenoico/farmacologia
Transportador de Glucose Tipo 2/genética
Transportador de Glucose Tipo 2/metabolismo
Proteínas de Homeodomínio/genética
Proteínas de Homeodomínio/metabolismo
Fator 2 Relacionado a NF-E2/genética
Fator 2 Relacionado a NF-E2/metabolismo
NF-kappa B/genética
NF-kappa B/metabolismo
Óxido Nítrico Sintase Tipo II/genética
Óxido Nítrico Sintase Tipo II/metabolismo
Pâncreas/citologia
Pâncreas/efeitos dos fármacos
Ratos
Ratos Wistar
Transativadores/genética
Transativadores/metabolismo
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/metabolismo
Ácido gama-Linolênico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Glucose Transporter Type 2); 0 (Homeodomain Proteins); 0 (Lipoxins); 0 (NF-E2-Related Factor 2); 0 (NF-kappa B); 0 (Nfe2l2 protein, rat); 0 (Slc2a2 protein, rat); 0 (Trans-Activators); 0 (Tumor Necrosis Factor-alpha); 0 (lipoxin A4); 0 (pancreatic and duodenal homeobox 1 protein); 0 (resolvin D2); 25167-62-8 (Docosahexaenoic Acids); 27YG812J1I (Arachidonic Acid); 78YC2MAX4O (gamma-Linolenic Acid); AAN7QOV9EA (Eicosapentaenoic Acid); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nos2 protein, rat); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (Ptgs2 protein, rat)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170301
[St] Status:MEDLINE


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[PMID]:28218420
[Au] Autor:Fedirko V; McKeown-Eyssen G; Serhan CN; Barry EL; Sandler RS; Figueiredo JC; Ahnen DJ; Bresalier RS; Robertson DJ; Anderson CW; Baron JA
[Ad] Endereço:Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, Georgia.
[Ti] Título:Plasma lipoxin A and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas.
[So] Source:Mol Carcinog;56(8):1977-1983, 2017 Aug.
[Is] ISSN:1098-2744
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A (LXA ) and resolvin D1(RvD1)] with risk for recurrent adenoma. In this pilot study, we used data and biosamples from an adenoma chemoprevention study investigating the effects of aspirin and/or folic acid on the occurrence of colorectal adenomas. In the parent study, 1121 participants with a recent adenoma were randomized to study agents to be taken until the next surveillance colonoscopy about 3 years later. In this pilot study, LXA and RvD1 from samples taken near the end of study treatment were measured in a randomly selected sub-set of 200 participants. Commercially available ELISA kits to assay the analytes were validated using a metabololipidomic LC-MS/MS assay. Poisson regression with a robust error variance was used to calculate risk ratios and 95% confidence intervals. Plasma LXA and RvD1 were not associated with the risk of adenoma occurrence. LXA at the end of study follow-up was 32% (P = 0.01) proportionately higher in women compared to men. A similar non-significant trend toward higher levels among women was observed for RvD1. Our preliminary findings provided no evidence that plasma LXA or RvD1 are associated with reduced risk of colorectal adenoma occurrence, but suggest LXA may differ among men and women. Future studies focusing on SPM's local effects and levels in the colon are needed.
[Mh] Termos MeSH primário: Adenoma/prevenção & controle
Anti-Inflamatórios não Esteroides/uso terapêutico
Aspirina/uso terapêutico
Neoplasias Colorretais/prevenção & controle
Ácidos Docosa-Hexaenoicos/sangue
Ácido Fólico/uso terapêutico
Lipoxinas/sangue
Complexo Vitamínico B/uso terapêutico
[Mh] Termos MeSH secundário: Adenoma/sangue
Adenoma/epidemiologia
Idoso
Colo/efeitos dos fármacos
Neoplasias Colorretais/sangue
Neoplasias Colorretais/epidemiologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Projetos Piloto
Reto/efeitos dos fármacos
Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Lipoxins); 0 (lipoxin A4); 0 (resolvin D1); 12001-76-2 (Vitamin B Complex); 25167-62-8 (Docosahexaenoic Acids); 935E97BOY8 (Folic Acid); R16CO5Y76E (Aspirin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE
[do] DOI:10.1002/mc.22629


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[PMID]:28209487
[Au] Autor:Liu C; Guan H; Cai C; Li F; Xiao J
[Ad] Endereço:Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, China.
[Ti] Título:Lipoxin A4 suppresses osteoclastogenesis in RAW264.7 cells and prevents ovariectomy-induced bone loss.
[So] Source:Exp Cell Res;352(2):293-303, 2017 Mar 15.
[Is] ISSN:1090-2422
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lipoxin A4 (LXA4; 5S, 6R, 15Strihydroxy- 7,9,13-trans-11-eicosatetraenoic acid) is a metabolic product of arachidonic acid under the action of lipoxidase. This lipid molecule plays important roles in several biological functions, especially inflammatory processes. In vivo, LXA4 regulates the inflammatory response through several signaling pathways. Its mechanism suggests that it might have an effect on osteoclastogenesis and bone loss. Using both in vitro and in vivo studies, it was here observed that LXA4 could significantly inhibit the formation and function of osteoclasts and these effects could be blocked by Boc-2, the specific inhibitor of FPR2/ALX (the receptor of LXA4). Meanwhile, LXA4 reduce the amount of ovariectomy-induced bone loss. These protective effects was found to be associated with inhibition of nuclear factor-κB (NF-κB), activator protein-1 (AP-1), PI3K-AKT, and p-38, ERK, and JNK in MAPKs. The expression of the receptor activator of the NF-κB ligand RANKL:osteoprotegerin ratio and serum levels of TNF-α, IL-1ß, and IL-6 were decreased by LXA4. Moreover, LXA4 prevented the production of reactive oxygen species (ROS), the expression of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP), cathepsin K (CK), matrix metalloproteinase (MMP)-9, RANK, and osteoclastic related transcription factors of c-Fos, NFATc1 could also be significantly inhibited by LXA4 in a dose-dependent manner. Studies have demonstrated that LXA4 can inhibit the formation and function of osteoclasts through modulation of several pathways both upstream and downstream of RANKL signaling and FPR2/ALX was involved in the procedures. This shows that LXA4 may be used as a new strategy for the treatment of osteoclast-related diseases.
[Mh] Termos MeSH primário: Reabsorção Óssea/metabolismo
Lipoxinas/farmacologia
Osteoporose Pós-Menopausa/metabolismo
[Mh] Termos MeSH secundário: Animais
Reabsorção Óssea/prevenção & controle
Catepsina K/genética
Catepsina K/metabolismo
Linhagem Celular
Feminino
Seres Humanos
Lipoxinas/uso terapêutico
Sistema de Sinalização das MAP Quinases
Metaloproteinase 9 da Matriz/genética
Metaloproteinase 9 da Matriz/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
NF-kappa B/metabolismo
Osteoclastos/efeitos dos fármacos
Osteoclastos/metabolismo
Osteoporose Pós-Menopausa/etiologia
Osteoporose Pós-Menopausa/prevenção & controle
Ovariectomia/efeitos adversos
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Ligante RANK/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Fosfatase Ácida Resistente a Tartarato/genética
Fosfatase Ácida Resistente a Tartarato/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipoxins); 0 (NF-kappa B); 0 (RANK Ligand); 0 (Reactive Oxygen Species); 0 (lipoxin A4); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.3.2 (Acp5 protein, mouse); EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase); EC 3.4.22.38 (Cathepsin K); EC 3.4.24.35 (Matrix Metalloproteinase 9); EC 3.4.24.35 (Mmp9 protein, mouse)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170218
[St] Status:MEDLINE



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