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[PMID]:28458362
[Au] Autor:Tanaka K; Yoshitomi T; Hirahara K
[Ad] Endereço:Biologics & Immuno-Oncology Laboratories, Daiichi Sankyo Co., Ltd.
[Ti] Título:Elucidation of Distinct Roles of Guinea Pig CXCR1 and CXCR2 in Neutrophil Migration toward IL-8 and GROα by Specific Antibodies.
[So] Source:Biol Pharm Bull;40(5):729-732, 2017.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Chemokine receptors CXCR1 and CXCR2 are conserved between guinea pigs and humans, but the distinct role of each receptor in chemotactic responses of neutrophils against chemokine ligands has not been elucidated due in part to the lack of specific inhibitors against these receptors in guinea pigs. In this study, we investigated the roles of guinea pig CXCR1 and CXCR2 on neutrophils in chemotactic responses to guinea pig interleukin (IL)-8 and growth-regulated oncogene (GRO)α by using specific inhibitory antibodies against these receptors. Neutrophil migration induced by IL-8 was partially inhibited by either anti-CXCR1 antibody or anti-CXCR2 antibody. In addition, the migration was inhibited completely when both anti-CXCR1 and anti-CXCR2 antibodies were combined. On the other hand, neutrophil migration induced by GROα was not inhibited by anti-CXCR1 antibody while inhibited profoundly by anti-CXCR2 antibody. These results indicated that CXCR1 and CXCR2 mediated migration induced by the IL-8 synergistically and only CXCR2 mediated migration induced by GROα in guinea pig neutrophils. Our findings on ligand selectivity of CXCR1 and CXCR2 in guinea pigs are consistent with those in humans.
[Mh] Termos MeSH primário: Quimiocina CXCL1/farmacologia
Interleucina-8/farmacologia
Neutrófilos/fisiologia
Receptores de Interleucina-8A/fisiologia
Receptores de Interleucina-8B/fisiologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Bloqueadores/farmacologia
Movimento Celular/efeitos dos fármacos
Quimiocina CXCL1/antagonistas & inibidores
Quimiotaxia/efeitos dos fármacos
Feminino
Cobaias
Doenças do Sistema Imune
Interleucina-8/antagonistas & inibidores
Transtornos Leucocíticos
Neutrófilos/imunologia
Receptores de Interleucina-8A/imunologia
Receptores de Interleucina-8B/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Blocking); 0 (Chemokine CXCL1); 0 (Interleukin-8); 0 (Receptors, Interleukin-8A); 0 (Receptors, Interleukin-8B)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b16-00918


  2 / 970 MEDLINE  
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[PMID]:29262362
[Au] Autor:Park SH; Berkamp S; Radoicic J; De Angelis AA; Opella SJ
[Ad] Endereço:Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California.
[Ti] Título:Interaction of Monomeric Interleukin-8 with CXCR1 Mapped by Proton-Detected Fast MAS Solid-State NMR.
[So] Source:Biophys J;113(12):2695-2705, 2017 Dec 19.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human chemokine interleukin-8 (IL-8; CXCL8) is a key mediator of innate immune and inflammatory responses. This small, soluble protein triggers a host of biological effects upon binding and activating CXCR1, a G protein-coupled receptor, located in the cell membrane of neutrophils. Here, we describe H-detected magic angle spinning solid-state NMR studies of monomeric IL-8 (1-66) bound to full-length and truncated constructs of CXCR1 in phospholipid bilayers under physiological conditions. Cross-polarization experiments demonstrate that most backbone amide sites of IL-8 (1-66) are immobilized and that their chemical shifts are perturbed upon binding to CXCR1, demonstrating that the dynamics and environments of chemokine residues are affected by interactions with the chemokine receptor. Comparisons of spectra of IL-8 (1-66) bound to full-length CXCR1 (1-350) and to N-terminal truncated construct NT-CXCR1 (39-350) identify specific chemokine residues involved in interactions with binding sites associated with N-terminal residues (binding site-I) and extracellular loop and helical residues (binding site-II) of the receptor. Intermolecular paramagnetic relaxation enhancement broadening of IL-8 (1-66) signals results from interactions of the chemokine with CXCR1 (1-350) containing Mn chelated to an unnatural amino acid assists in the characterization of the receptor-bound form of the chemokine.
[Mh] Termos MeSH primário: Interleucina-8/química
Interleucina-8/metabolismo
Ressonância Magnética Nuclear Biomolecular
Receptores de Interleucina-8A/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Bicamadas Lipídicas/metabolismo
Modelos Moleculares
Ligação Proteica
Conformação Proteica
Receptores de Interleucina-8A/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-8); 0 (Lipid Bilayers); 0 (Receptors, Interleukin-8A)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE


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[PMID]:29066305
[Au] Autor:Gond DP; Singh S; Agrawal NK
[Ad] Endereço:Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
[Ti] Título:Testing an association between TLR4 and CXCR1 gene polymorphisms with susceptibility to urinary tract infection in type 2 diabetes in north Indian population.
[So] Source:Gene;641:196-202, 2018 Jan 30.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Genetic variations of Toll like receptor 4 (TLR4) and CXC-chemokine receptor type1 (CXCR1), the key elements of innate immune system and their association with urinary tract infection (UTI) were studied in general population. In present study we investigate genetic variation of these genes in diabetic patients (3 to 4 times higher prevalence of UTI in comparison to general population). METHODS: A total 1100 subjects (318 diabetic patients with UTI, 324 diabetic patients without UTI, 200 non-diabetic UTI patients and 260 age matched healthy control) were enrolled in the study. SNPs of TLR4 rs4986790, rs4986791 and CXCR1 rs2234671 was assessed by PCR-RFLP and PCR-SSP respectively. RESULTS: Statistical analysis revealed that A/G genotype and G allele of TLR4 rs4986790 are significantly associated with UTI in both diabetics and nondiabetic patients in comparison to healthy control. Similarly CT genotype and T allele of TLR4 rs4986791 are also significantly associated with UTI in both groups. We also found that prevalence of A/G genotype of TLR4 rs4986790 and CT genotype of TLR4 rs4986791 are significantly higher in patients of diabetes with UTI in comparison to diabetic patients without UTI. We did not find any association of CXCR1 rs2234671 polymorphism with UTI by comparing with any group. CONCLUSION: We found that TLR4 rs4986790 and rs4986791 gene polymorphism is a risk for UTI development in both diabetic and nondiabetic patients in north Indian population.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/genética
Predisposição Genética para Doença/genética
Polimorfismo de Nucleotídeo Único/genética
Receptores de Interleucina-8A/genética
Receptor 4 Toll-Like/genética
Infecções Urinárias/genética
[Mh] Termos MeSH secundário: Adulto
Alelos
Estudos de Casos e Controles
Feminino
Genótipo
Seres Humanos
Índia
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Interleukin-8A); 0 (TLR4 protein, human); 0 (Toll-Like Receptor 4)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171026
[St] Status:MEDLINE


  4 / 970 MEDLINE  
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[PMID]:28705839
[Au] Autor:Gloude NJ; Khandelwal P; Luebbering N; Lounder DT; Jodele S; Alder MN; Lane A; Wilkey A; Lake KE; Litts B; Davies SM
[Ad] Endereço:Division of Bone Marrow Transplantation and Immune Deficiency and.
[Ti] Título:Circulating dsDNA, endothelial injury, and complement activation in thrombotic microangiopathy and GVHD.
[So] Source:Blood;130(10):1259-1266, 2017 Sep 07.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transplant-associated thrombotic microangiopathy (TA-TMA) is a common and poorly recognized complication of hematopoietic stem cell transplantation (HSCT) associated with excessive complement activation, likely triggered by endothelial injury. An important missing piece is the link between endothelial injury and complement activation. We hypothesized that neutrophil extracellular traps (NETs) mechanistically link endothelial damage with complement activation and subsequent TA-TMA. Neutrophil activation releases granule proteins together with double-stranded DNA (dsDNA) to form extracellular fibers known as NETs. NETs have been shown to activate complement and can be assessed in humans by quantification of dsDNA in serum. We measured levels of dsDNA, as a surrogate for NETs in 103 consecutive pediatric allogeneic transplant recipients at day 0, +14, +30, +60, and +100. A spike in dsDNA production around day +14 during engraftment was associated with subsequent TA-TMA development. Peak dsDNA production around day +14 was associated with interleukin-8-driven neutrophil recovery. Increased dsDNA levels at days +30, +60, and +100 were also associated with increased mortality and gastrointestinal graft-versus-host disease (GVHD). NETs may serve as a mechanistic link between endothelial injury and complement activation. NET formation may be one mechanism contributing to the clinical overlap between GVHD and TA-TMA.
[Mh] Termos MeSH primário: Ativação do Complemento/imunologia
DNA/sangue
Células Endoteliais/patologia
Doença Enxerto-Hospedeiro/sangue
Doença Enxerto-Hospedeiro/imunologia
Microangiopatias Trombóticas/sangue
Microangiopatias Trombóticas/imunologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Pré-Escolar
Demografia
Armadilhas Extracelulares/metabolismo
Doença Enxerto-Hospedeiro/etiologia
Doença Enxerto-Hospedeiro/patologia
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Seres Humanos
Lactente
Interleucina-8/metabolismo
Estudos Longitudinais
Neutrófilos/metabolismo
Receptores de Interleucina-8A/metabolismo
Receptores de Interleucina-8B/metabolismo
Microangiopatias Trombóticas/etiologia
Microangiopatias Trombóticas/terapia
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-8); 0 (Receptors, Interleukin-8A); 0 (Receptors, Interleukin-8B); 9007-49-2 (DNA)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-05-782870


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[PMID]:28666021
[Au] Autor:Romano A; Carneiro MBH; Doria NA; Roma EH; Ribeiro-Gomes FL; Inbar E; Lee SH; Mendez J; Paun A; Sacks DL; Peters NC
[Ad] Endereço:Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
[Ti] Título:Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.
[So] Source:PLoS Pathog;13(6):e1006479, 2017 Jun.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammatory monocytes can be manipulated by environmental cues to perform multiple functions. To define the role of monocytes during primary or secondary infection with an intra-phagosomal pathogen we employed Leishmania major-red fluorescent protein (RFP) parasites and multi-color flow cytometry to define and enumerate infected and uninfected inflammatory cells in the skin. During primary infection, infected monocytes had altered maturation and were the initial mononuclear host cell for parasite replication. In contrast, at a distal site of secondary infection in mice with a healed but persistent primary infection, this same population rapidly produced inducible nitric oxide synthase (iNOS) in an IFN-γ dependent manner and was critical for parasite killing. Maturation to a dendritic cell-like phenotype was not required for monocyte iNOS-production, and enhanced monocyte recruitment correlated with IFN-γ dependent cxcl10 expression. In contrast, neutrophils appeared to be a safe haven for parasites in both primary and secondary sites. Thus, inflammatory monocytes play divergent roles during primary versus secondary infection with an intra-phagosomal pathogen.
[Mh] Termos MeSH primário: Coinfecção/microbiologia
Leishmania major
Leishmaniose Cutânea/imunologia
Monócitos/microbiologia
Fagossomos/metabolismo
Pele/microbiologia
[Mh] Termos MeSH secundário: Animais
Antígenos Ly/imunologia
Coinfecção/imunologia
Células Dendríticas/metabolismo
Feminino
Inflamação/microbiologia
Leishmaniose Cutânea/parasitologia
Camundongos Transgênicos
Monócitos/metabolismo
Neutrófilos/metabolismo
Óxido Nítrico Sintase Tipo II/metabolismo
Fagossomos/imunologia
Receptores CCR2/imunologia
Receptores de Interleucina-8A/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Ly); 0 (Ccr2 protein, mouse); 0 (Ly6 protein, mouse); 0 (Receptors, CCR2); 0 (Receptors, Interleukin-8A); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nos2 protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170701
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006479


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[PMID]:28351983
[Au] Autor:Blaser BW; Moore JL; Hagedorn EJ; Li B; Riquelme R; Lichtig A; Yang S; Zhou Y; Tamplin OJ; Binder V; Zon LI
[Ad] Endereço:Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
[Ti] Título:CXCR1 remodels the vascular niche to promote hematopoietic stem and progenitor cell engraftment.
[So] Source:J Exp Med;214(4):1011-1027, 2017 Apr 03.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Recent advances marking fluorescent HSPCs have allowed exquisite visualization of HSPCs in the caudal hematopoietic tissue (CHT) of the developing zebrafish. Here, we show that the chemokine and its receptor, , are expressed by zebrafish endothelial cells, and we identify signaling as a positive regulator of HSPC colonization. Single-cell tracking experiments demonstrated that this is a result of increases in HSPC-endothelial cell "cuddling," HSPC residency time within the CHT, and HSPC mitotic rate. Enhanced signaling was associated with an increase in the volume of the CHT and induction of expression. Finally, using parabiotic zebrafish, we show that acts HSPC nonautonomously to improve the efficiency of donor HSPC engraftment. This work identifies a mechanism by which the hematopoietic niche remodels to promote HSPC engraftment and suggests that signaling is a potential therapeutic target in patients undergoing hematopoietic stem cell transplantation.
[Mh] Termos MeSH primário: Transplante de Células-Tronco Hematopoéticas
Receptores de Interleucina-8A/fisiologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Microambiente Celular
Células-Tronco Hematopoéticas/fisiologia
Interleucina-8/fisiologia
Transdução de Sinais/fisiologia
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-8); 0 (Receptors, Interleukin-8A)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170330
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20161616


  7 / 970 MEDLINE  
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[PMID]:28320442
[Au] Autor:Parillaud VR; Lornet G; Monnet Y; Privat AL; Haddad AT; Brochard V; Bekaert A; de Chanville CB; Hirsch EC; Combadière C; Hunot S; Lobsiger CS
[Ad] Endereço:Inserm, U 1127, F-75013, Paris, France.
[Ti] Título:Analysis of monocyte infiltration in MPTP mice reveals that microglial CX3CR1 protects against neurotoxic over-induction of monocyte-attracting CCL2 by astrocytes.
[So] Source:J Neuroinflammation;14(1):60, 2017 Mar 21.
[Is] ISSN:1742-2094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Evidence from mice suggests that brain infiltrating immune cells contribute to neurodegeneration, and we previously identified a deleterious lymphocyte infiltration in Parkinson's disease mice. However, this remains controversial for monocytes, due to artifact-prone techniques used to distinguish them from microglia. Our aim was to reassess this open question, by taking advantage of the recent recognition that chemokine receptors CCR2 and CX3CR1 can differentiate between inflammatory monocytes and microglia, enabling to test whether CCR2 monocytes infiltrate the brain during dopaminergic (DA) neurodegeneration and whether they contribute to neuronal death. This revealed unexpected insights into possible regulation of monocyte-attracting CCL2 induction. METHODS: We used acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice and assessed monocyte infiltration by combining laser microdissection-guided chemokine RNA profiling of the substantia nigra (SN) with immunohistochemistry and CCR2-GFP reporter mice. To determine contribution to neuronal loss, we used CCR2-deletion and CCL2-overexpression, to reduce and increase CCR2 monocyte infiltration, and CX3CR1-deletion to assess a potential implication in CCL2 regulation. RESULTS: Nigral chemokine profiling revealed early CCL2/7/12-CCR2 axis induction, suggesting monocyte infiltration in MPTP mice. CCL2 protein showed early peak induction in nigral astrocytes, while CCR2-GFP mice revealed early but limited nigral monocyte infiltration. However, blocking infiltration by CCR2 deletion did not influence DA neuronal loss. In contrast, transgenic astrocytic CCL2 over-induction increased CCR2 monocyte infiltration and DA neuronal loss in MPTP mice. Surprisingly, CCL2 over-induction was also detected in MPTP intoxicated CX3CR1-deleted mice, which are known to present increased DA neuronal loss. Importantly, CX3CR1/CCL2 double-deletion suggested that increased neurotoxicity was driven by astrocytic CCL2 over-induction. CONCLUSIONS: We show that CCR2 monocytes infiltrate the affected CNS, but at the level observed in acute MPTP mice, this does not contribute to DA neuronal loss. In contrast, the underlying astrocytic CCL2 induction seemed to be tightly controled, as already moderate CCL2 over-induction led to increased neurotoxicity in MPTP mice, likely due to the increased CCR2 monocyte infiltration. Importantly, we found evidence suggesting that during DA neurodegeneration, this control was mediated by microglial CX3CR1 signaling, which protects against such neurotoxic CCL2 over-induction by astrocytes, thus hinting at an endogenous mechanism to limit neurotoxic effects of the CCL2-CCR2 axis.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Movimento Celular/efeitos dos fármacos
Quimiocina CCL2/metabolismo
Intoxicação por MPTP/patologia
Microglia/metabolismo
Receptores de Interleucina-8A/deficiência
[Mh] Termos MeSH secundário: Animais
Astrócitos/efeitos dos fármacos
Antígeno CD11b/metabolismo
Proteínas de Ligação ao Cálcio/metabolismo
Movimento Celular/genética
Modelos Animais de Doenças
Regulação da Expressão Gênica/efeitos dos fármacos
Lipopolissacarídeos/farmacologia
Intoxicação por MPTP/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Proteínas dos Microfilamentos/metabolismo
Microglia/efeitos dos fármacos
Monócitos/efeitos dos fármacos
Monócitos/metabolismo
Receptores CCR2/genética
Receptores CCR2/metabolismo
Receptores de Interleucina-8A/genética
Substância Negra/efeitos dos fármacos
Substância Negra/patologia
Fatores de Tempo
Tirosina 3-Mono-Oxigenase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aif1 protein, mouse); 0 (CD11b Antigen); 0 (Calcium-Binding Proteins); 0 (Ccl2 protein, mouse); 0 (Ccr2 protein, mouse); 0 (Chemokine CCL2); 0 (Lipopolysaccharides); 0 (Microfilament Proteins); 0 (Receptors, CCR2); 0 (Receptors, Interleukin-8A); EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1186/s12974-017-0830-9


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[PMID]:28129639
[Au] Autor:Kemp DM; Pidich A; Larijani M; Jonas R; Lash E; Sato T; Terai M; De Pizzol M; Allegretti M; Igoucheva O; Alexeev V
[Ad] Endereço:Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA.
[Ti] Título:Ladarixin, a dual CXCR1/2 inhibitor, attenuates experimental melanomas harboring different molecular defects by affecting malignant cells and tumor microenvironment.
[So] Source:Oncotarget;8(9):14428-14442, 2017 Feb 28.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CXCR1 and CXCR2 chemokine receptors and their ligands (CXCL1/2/3/7/8) play an important role in tumor progression. Tested to date CXCR1/2 antagonists and chemokine-targeted antibodies were reported to affect malignant cells in vitro and in animal models. Yet, redundancy of chemotactic signals and toxicity hinder further clinical development of these approaches. In this pre-clinical study we investigated the capacity of a novel small molecule dual CXCR1/2 inhibitor, Ladarixin (LDX), to attenuate progression of experimental human melanomas. Our data showed that LDX-mediated inhibition of CXCR1/2 abrogated motility and induced apoptosis in cultured cutaneous and uveal melanoma cells and xenografts independently of the molecular defects associated with the malignant phenotype. These effects were mediated by the inhibition of AKT and NF-kB signaling pathways. Moreover, systemic treatment of melanoma-bearing mice with LDX also polarized intratumoral macrophages to M1 phenotype, abrogated intratumoral de novo angiogenesis and inhibited melanoma self-renewal. Collectively, these studies outlined the pre-requisites of the successful CXCR1/2 inhibition on malignant cells and demonstrated multifactorial effects of Ladarixin on cutaneous and uveal melanomas, suggesting therapeutic utility of LDX in treatment of various melanoma types.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Melanoma Experimental/tratamento farmacológico
Receptores de Interleucina-8A/antagonistas & inibidores
Receptores de Interleucina-8B/antagonistas & inibidores
Sulfonamidas/farmacologia
Microambiente Tumoral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Western Blotting
Adesão Celular/efeitos dos fármacos
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Quimiotaxia
Seres Humanos
Interleucina-8/metabolismo
Melanoma Experimental/metabolismo
Melanoma Experimental/patologia
Camundongos
Camundongos Nus
NF-kappa B
Neovascularização Patológica/tratamento farmacológico
Neovascularização Patológica/metabolismo
Neovascularização Patológica/patologia
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Transdução de Sinais
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide); 0 (Antineoplastic Agents); 0 (Interleukin-8); 0 (NF-kappa B); 0 (RNA, Messenger); 0 (Receptors, Interleukin-8A); 0 (Receptors, Interleukin-8B); 0 (Sulfonamides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.14803


  9 / 970 MEDLINE  
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[PMID]:27780937
[Au] Autor:Cao Y; Liu H; Zhang H; Lin C; Li R; Wu S; Li H; He H; Zhang W; Xu J
[Ad] Endereço:Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
[Ti] Título:CXC chemokine receptor 1 predicts postoperative prognosis and chemotherapeutic benefits for TNM II and III resectable gastric cancer patients.
[So] Source:Oncotarget;8(12):20328-20339, 2017 Mar 21.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Backround: Abnormal expression of CXC chemokine receptor 1 (CXCR1) has shown the ability to promote tumor angiogensis, invasion and metastasis in several cancers. The purpose of our curret study is to discover the clinical prognostic significance of CXCR1 in resectable gastric cancer. METHODS: 330 gastric cancer patients who underwent R0 gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital, Fudan University between 2007 and 2008 were enrolled. CXCR1 expression was evaluated with use of immunohistochemical staining. The relation between CXCR1 expression and clinicopathological features and postoperative prognosis was respectively inspected. RESULTS: In both discovery and validation data sets, CXCR1 high expression indicated poorer overall survival (OS) in TNM II and III patients. Furthermore, multivariate analysis identified CXCR1 expression and TNM stage as two independent prognostic factors for OS. Incorporating CXCR1 expression into current TNM staging system could generate a novel clinical predictive model for gastric cancer, showing better prognostic accuracy with respect to patients' OS. More importantly, TNM II patients with higher CXCR1 expression were shown to significantly benefit from postoperative 5-fluorouracil (5-FU) based adjuvant chemotherapy (ACT). CONCLUSION: CXCR1 in gastric cancer was identified as an independent adverse prognostic factor. Combining CXCR1 expression with current TNM staging system could lead to better risk stratification and more accurate prognosis for gastric cancer patients. High expression of CXCR1 identified a subgroup of TNM stage II gastric cancer patients who appeared to benefit from 5-FU based ACT.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Receptores de Interleucina-8A/metabolismo
Neoplasias Gástricas/patologia
Neoplasias Gástricas/terapia
[Mh] Termos MeSH secundário: Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Quimioterapia Adjuvante
Feminino
Fluoruracila/administração & dosagem
Gastrectomia
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Estadiamento de Neoplasias
Período Pós-Operatório
Prognóstico
Receptores de Interleucina-8A/análise
Neoplasias Gástricas/mortalidade
Análise Serial de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Receptors, Interleukin-8A); U3P01618RT (Fluorouracil)
[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:161027
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.12815


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[PMID]:27496101
[Au] Autor:Williams AE; José RJ; Mercer PF; Brealey D; Parekh D; Thickett DR; O'Kane C; McAuley DF; Chambers RC
[Ad] Endereço:Division of Medicine, Centre for Inflammation and Tissue Repair, UCL Respiratory, Rayne Institute, University College London (UCL), London, UK.
[Ti] Título:Evidence for chemokine synergy during neutrophil migration in ARDS.
[So] Source:Thorax;72(1):66-73, 2017 Jan.
[Is] ISSN:1468-3296
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space. OBJECTIVES: The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. METHODS: CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry. RESULTS: CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS. CONCLUSION: This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS.
[Mh] Termos MeSH primário: Quimiocina CCL2/metabolismo
Quimiocina CCL7/metabolismo
Quimiotaxia de Leucócito
Interleucina-8/metabolismo
Neutrófilos/fisiologia
Síndrome do Desconforto Respiratório do Adulto/metabolismo
[Mh] Termos MeSH secundário: Adulto
Anticorpos Neutralizantes/farmacologia
Líquido da Lavagem Broncoalveolar/química
Quimiocina CCL2/antagonistas & inibidores
Quimiocina CCL7/antagonistas & inibidores
Quimiotaxia de Leucócito/efeitos dos fármacos
Voluntários Saudáveis
Seres Humanos
Interleucina-8/antagonistas & inibidores
Lipopolissacarídeos
Proteínas de Membrana/metabolismo
Neutrófilos/metabolismo
Receptores CCR2/metabolismo
Receptores de Interleucina-8A/metabolismo
Síndrome do Desconforto Respiratório do Adulto/imunologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (CCL2 protein, human); 0 (CCL7 protein, human); 0 (CCR2 protein, human); 0 (Chemokine CCL2); 0 (Chemokine CCL7); 0 (IL8 protein, human); 0 (Interleukin-8); 0 (Lipopolysaccharides); 0 (Membrane Proteins); 0 (Receptors, CCR2); 0 (Receptors, Interleukin-8A)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160807
[St] Status:MEDLINE
[do] DOI:10.1136/thoraxjnl-2016-208597



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