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[PMID]:28467378
[Au] Autor:Ali L; Goraya MU; Arafat Y; Ajmal M; Chen JL; Yu D
[Ad] Endereço:College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. liaqatpaksw@yahoo.com.
[Ti] Título:Molecular Mechanism of Quorum-Sensing in Enterococcus faecalis: Its Role in Virulence and Therapeutic Approaches.
[So] Source:Int J Mol Sci;18(5), 2017 May 03.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Quorum-sensing systems control major virulence determinants in , which causes nosocomial infections. The . quorum-sensing systems include several virulence factors that are regulated by the operon, which encodes the cytolysin toxin. In addition, the . Fsr regulator system controls the expression of gelatinase, serine protease, and enterocin O16. The cytolysin and Fsr virulence factor systems are linked to enterococcal diseases that affect the health of humans and other host models. Therefore, there is substantial interest in understanding and targeting these regulatory pathways to develop novel therapies for enterococcal infection control. Quorum-sensing inhibitors could be potential therapeutic agents for attenuating the pathogenic effects of . . Here, we discuss the regulation of cytolysin, the LuxS system, and the Fsr system, their role in . -mediated infections, and possible therapeutic approaches to prevent . infection.
[Mh] Termos MeSH primário: Infecção Hospitalar/microbiologia
Enterococcus faecalis/patogenicidade
Infecções por Bactérias Gram-Positivas/microbiologia
Percepção de Quorum/fisiologia
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Antibacterianos/uso terapêutico
Proteínas de Bactérias/genética
Biofilmes/efeitos dos fármacos
Biofilmes/crescimento & desenvolvimento
Liases de Carbono-Enxofre/genética
Infecção Hospitalar/tratamento farmacológico
Enterococcus faecalis/efeitos dos fármacos
Enterococcus faecalis/genética
Regulação Bacteriana da Expressão Gênica/fisiologia
Infecções por Bactérias Gram-Positivas/tratamento farmacológico
Seres Humanos
Perforina/genética
Percepção de Quorum/efeitos dos fármacos
Virulência
Fatores de Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Virulence Factors); 126465-35-8 (Perforin); EC 4.4.- (Carbon-Sulfur Lyases); EC 4.4.1.21 (LuxS protein, Bacteria)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


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[PMID]:28743062
[Au] Autor:Sanad EF; Hamdy NM; El-Etriby AK; Sebak SA; El-Mesallamy HO
[Ad] Endereço:Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, 11566 Cairo, Egypt.
[Ti] Título:Peripheral leucocytes and tissue gene expression of granzyme B/perforin system and serpinB9: Impact on inflammation and insulin resistance in coronary atherosclerosis.
[So] Source:Diabetes Res Clin Pract;131:132-141, 2017 Sep.
[Is] ISSN:1872-8227
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:AIM: The imbalance between proapoptotic granzyme B (GZB)/perforin (PRF) system and proteinase inhibitor-9 (PI-9; serpinB9); the only known inhibitor of human GZB, has been demonstrated in atherosclerosis. However, their role in atherosclerosis with the impact of type 2 diabetes mellitus (DM) as well as their contribution to hallmarks of atherosclerosis is not clear. SUBJECTS AND METHODS: ELISA for serum insulin, high sensitivity C-reactive protein (hsCRP) and GZB levels in atherosclerotic coronary artery diseases (CAD) patients were estimated in comparison to apparently healthy controls, while GZB, PRF and PI-9 mRNA expression levels were quantified by Taqman RT-PCR in both peripheral leucocytes and atherosclerotic tissues. RESULTS: Atherosclerotic patients showed significantly higher insulin, hsCRP and GZB levels than controls. There was a significant increase in GZB mRNA expression and significant reduction in PI-9 mRNA in both patient peripheral leucocytes and atherosclerotic lesions, while PRF mRNA increased significantly only in atherosclerotic tissues. PI-9 mRNA levels were significantly lower in patients with diabetes than patients without diabetes. In contrast to positive modulating effect of GZB, regression analysis revealed negative modulating effect of PI-9 on inflammation and insulin resistance. Circulating PI-9 mRNA was inversely contributed to CAD severity. CONCLUSIONS: GZB and PI-9 could be effective modulators for inflammation and insulin resistance in atherosclerosis.
[Mh] Termos MeSH primário: Aterosclerose/genética
Doença da Artéria Coronariana/genética
Granzimas/metabolismo
Inflamação/metabolismo
Resistência à Insulina/fisiologia
Leucócitos/metabolismo
Perforina/metabolismo
Proteínas Recombinantes de Fusão/metabolismo
Serpinas/metabolismo
[Mh] Termos MeSH secundário: Idoso
Aterosclerose/metabolismo
Doença da Artéria Coronariana/metabolismo
Feminino
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Fusion Proteins); 0 (Serpins); 126465-35-8 (Perforin); EC 3.4.21.- (Granzymes); EC 3.4.21.- (perforin-granzyme B)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE


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[PMID]:29261698
[Au] Autor:Nehete PN; Shelton KA; Nehete BP; Chitta S; Williams LE; Schapiro SJ; Abee CR
[Ad] Endereço:Department of Veterinary Sciences, The University of Texas MD Anderson Cancer Center, Bastrop, Texas, United States of America.
[Ti] Título:Effects of transportation, relocation, and acclimation on phenotypes and functional characteristics of peripheral blood lymphocytes in rhesus monkeys (Macaca mulatta).
[So] Source:PLoS One;12(12):e0188694, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nonhuman primates from domestic sources constitute a small, but critical, proportion of animals studied in research laboratories. Many of these nonhuman primates are raised at one facility and subsequently transported/relocated to another facility for research purposes. We examined the effects of transport, relocation, and acclimation on the phenotype and function of peripheral blood mononuclear cells (PBMCs) in a group of rhesus monkeys that were transported by road for approximately 21 hours from one facility to another. Using a panel of human antibodies and a set of standardized human immune assays, we evaluated the phenotype of lymphocyte subsets by flow, mitogen-specific immune responses of PBMCs in vitro, and levels of circulating cytokines and cortisol in plasma at various time points including immediately before transport, immediately upon arrival, and after approximately 30 days of acclimation. Analyses of blood samples revealed that CD3+ T-cell and CD20+ B-cell populations had decreased significantly immediately after relocation but had recovered within 30 days after arrival at the new facility. Similarly, circulating cortisol and cytokine levels in plasma were significantly higher immediately after relocation; and by the 30-day time point, these differences were no longer significant. However, immune assays of PBMCs indicated that mitogen-specific responses for proliferation, interferon γ (IFN-γ), and perforin were significantly higher after relocation and 30 days of acclimation. These findings have implications on the research participation of transported and relocated nonhuman primates in immunologic research studies, suggesting that 30 days is not sufficient to ensure return to baseline immune homeostasis. These data should be considered when planning research studies in order to minimize potential confounding factors associated with relocation and to maximize study validity.
[Mh] Termos MeSH primário: Aclimatação
Linfócitos/fisiologia
Transportes
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Proliferação Celular/efeitos dos fármacos
Citocinas/sangue
ELISPOT
Feminino
Hidrocortisona/sangue
Interferon gama/metabolismo
Subpopulações de Linfócitos/efeitos dos fármacos
Subpopulações de Linfócitos/fisiologia
Linfócitos/efeitos dos fármacos
Macaca mulatta
Masculino
Mitógenos/farmacologia
Perforina/metabolismo
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 0 (Mitogens); 126465-35-8 (Perforin); 82115-62-6 (Interferon-gamma); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188694


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[PMID]:28468610
[Au] Autor:Bordbar MR; Modarresi F; Farazi Fard MA; Dastsooz H; Shakib Azad N; Faghihi MA
[Ad] Endereço:Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
[Ti] Título:A case report of novel mutation in PRF1 gene, which causes familial autosomal recessive hemophagocytic lymphohistiocytosis.
[So] Source:BMC Med Genet;18(1):49, 2017 05 03.
[Is] ISSN:1471-2350
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening immunodeficiency and multi-organ disease that affects people of all ages and ethnic groups. Common symptoms and signs of this disease are high fever, hepatosplenomegaly, and cytopenias. Familial form of HLH disease, which is an autosomal recessive hematological disorder is due to disease-causing mutations in several genes essential for NK and T-cell granule-mediated cytotoxic function. For an effective cytotoxic response from cytotoxic T lymphocyte or NK cell encountering an infected cell or tumor cell, different processes are required, including trafficking, docking, priming, membrane fusion, and entry of cytotoxic granules into the target cell leading to apoptosis. Therefore, genes involved in these steps play important roles in the pathogenesis of HLH disease which include PRF1, UNC13D (MUNC13-4), STX11, and STXBP2 (MUNC18-2). CASE PRESENTATION: Here, we report a novel missense mutation in an 8-year-old boy suffered from hepatosplenomegaly, hepatitis, epilepsy and pancytopenia. The patient was born to a first-cousin parents with no previous documented disease in his parents. To identify mutated gene in the proband, Whole Exome Sequencing (WES) utilizing next generation sequencing was used on an Illumina HiSeq 2000 platform on DNA sample from the patient. Results showed a novel deleterious homozygous missense mutation in PRF1 gene (NM_001083116: exon3: c. 1120 T > G, p.W374G) in the patient and then using Sanger sequencing it was confirmed in the proband and his parents. Since his parents were heterozygous for the identified mutation, autosomal recessive pattern of inheritance was confirmed in the family. CONCLUSIONS: Our study identified a rare new pathogenic missense mutation in PRF1 gene in patient with HLH disease and it is the first report of mutation in PRF1 in Iranian patients with this disease.
[Mh] Termos MeSH primário: Genes Recessivos
Linfo-Histiocitose Hemofagocítica/genética
Mutação de Sentido Incorreto
Perforina/genética
[Mh] Termos MeSH secundário: Criança
Feminino
Seres Humanos
Linfo-Histiocitose Hemofagocítica/diagnóstico por imagem
Imagem por Ressonância Magnética
Masculino
Linhagem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (PRF1 protein, human); 126465-35-8 (Perforin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171231
[Lr] Data última revisão:
171231
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s12881-017-0404-9


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[PMID]:29040297
[Au] Autor:Zhu L; Aly M; Wang H; Karakizlis H; Weimer R; Morath C; Kuon RJ; Toth B; Opelz G; Daniel V
[Ad] Endereço:Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, Heidelberg, Germany.
[Ti] Título:Decreased NK cell immunity in kidney transplant recipients late post-transplant and increased NK-cell immunity in patients with recurrent miscarriage.
[So] Source:PLoS One;12(10):e0186349, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There is evidence that NK-cell reactivity might affect graft outcome in transplant recipients and pregnancy in women. METHOD: NK-cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients before and after renal transplantation, patients with recurrent miscarriage (RM) and healthy controls (HC). RESULTS: Patients late post-transplant (late-Tx) with functioning renal transplants showed abnormally low CD56dimCD16+ NK-cells containing both perforin and granzyme (vs HC p = 0.021) whereas RM patients exhibited abnormally high numbers of these cells (vs HC p = 0.043). CD56dimCD16+perforin+granzyme+ NK-cell counts were strikingly different between the two patient groups (p<0.001). In addition, recipients late-Tx showed abnormally low CD8+ NK-cells (vs HC p<0.001) in contrast to RM patients who showed an abnormal increase (vs HC p = 0.008). CD8+ NK-cell counts were strongly different between the two patient groups (p<0.001). Higher perforin+granzyme+CD56dimCD16+ and CD8+ NK-cells were associated with impaired graft function (p = 0.044, p = 0.032). After in-vitro stimulation, CD56dimCD16+ and CD56brightCD16dim/- NK-cells showed strong upregulation of CD107a and IFNy, whereas the content of perforin decreased dramatically as a consequence of perforin release. Recipients late post-Tx showed less in-vitro perforin release (= less cytotoxicity) than HC (p = 0.037) and lower perforin release was associated with good graft function (r = 0.738, p = 0.037). Notably, we observed strong in-vitro perforin release in 2 of 6 investigated RM patients. When circulating IL10+CD56bright NK-cells were analyzed, female recipients late post-Tx (n = 9) showed significantly higher relative and absolute cell numbers than RM patients (p = 0.002 and p = 0.018, respectively); and high relative and absolute IL10+CD56bright NK-cell numbers in transplant recipients were associated with low serum creatinine (p = 0.004 and p = 0.012) and high glomerular filtration rate (p = 0.011 and p = 0.002, respectively). Female recipients late post-Tx exhibited similar absolute but higher relative numbers of IL10+IFNy- NK-cells than RM patients (p>0.05 and p = 0.016, respectively). CONCLUSION: NK-cells with lower cytotoxicity and immunoregulatory function might contribute to good long-term graft outcome, whereas circulating NK-cells with normal or even increased cytotoxicity and less immunoregulatory capacity are observed in patients with RM.
[Mh] Termos MeSH primário: Aborto Habitual/sangue
Transplante de Rim/efeitos adversos
Rim/imunologia
Células Matadoras Naturais/imunologia
[Mh] Termos MeSH secundário: Aborto Habitual/imunologia
Aborto Habitual/patologia
Adulto
Idoso
Linfócitos T CD8-Positivos/imunologia
Feminino
Citometria de Fluxo
Taxa de Filtração Glomerular
Granzimas/sangue
Seres Humanos
Rim/metabolismo
Rim/patologia
Células Matadoras Naturais/patologia
Masculino
Meia-Idade
Perforina/sangue
Gravidez
Transplantados
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
126465-35-8 (Perforin); EC 3.4.21.- (Granzymes)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186349


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[PMID]:28926522
[Au] Autor:Hodge G; Hodge S; Yeo A; Nguyen P; Hopkins E; Holmes-Liew CL; Reynolds PN; Holmes M
[Ad] Endereço:1 Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia. 2 Department of Medicine, University of Adelaide, Adelaide, South Australia. 3 South Australian Lung Transplant Service, Adelaide, South Australia.
[Ti] Título:BOS Is Associated With Increased Cytotoxic Proinflammatory CD8 T, NKT-Like, and NK Cells in the Small Airways.
[So] Source:Transplantation;101(10):2469-2476, 2017 Oct.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Immunosuppression therapy after lung transplantation fails to prevent bronchiolitis obliterans syndrome (BOS) in many patients, primarily a disease of the small airways. We have reported that BOS is associated with a lack of suppression of cytotoxic mediators, and proinflammatory cytokines, in peripheral blood T, NKT-like (particularly CD8+) and NK cells. We also showed a loss of glucocorticoid receptor (GCR) in proinflammatory lymphocytes after transplant. It is unknown whether these proinflammatory lymphocytes target the small and/or large airways in BOS. METHODS: Blood, bronchoalveolar lavage, large proximal, and small distal airway brushings were collected from patients with BOS (n = 10), stable lung transplant patients (n = 18), and healthy aged-matched controls (n = 10). Intracellular cytotoxic mediators (perforin/granzyme B), proinflammatory cytokines (IFNγ/TNFα), and expression of GCR were determined in lymphocytes subsets from cultured blood using flow cytometry. RESULTS: Increases in CD8 T cells, NKT-like cells, and NK cells were found in the small distal airways in BOS compared with stable patients and controls. An increase in perforin, granzyme B, IFNγ, TNFα, and a loss of GCR from these lymphocyte subsets was also found in BOS. GCR expression by CD8+ T cells from small airways correlated with FEV1 (R = 0.834, P = 0.039). Many of these changes significantly differed from those in the large airways. CONCLUSIONS: BOS is associated with increased cytotoxic/proinflammatory CD8+ T, NKT-like, and NK cells in the small airways. Treatments that increase GCR in these lymphocyte subsets may improve graft survival.
[Mh] Termos MeSH primário: Brônquios/patologia
Bronquiolite Obliterante/imunologia
Linfócitos T CD8-Positivos/patologia
Imunidade Celular
Células Matadoras Naturais/patologia
Transplante de Pulmão/efeitos adversos
Perforina/biossíntese
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Biópsia
Brônquios/imunologia
Brônquios/metabolismo
Bronquiolite Obliterante/metabolismo
Bronquiolite Obliterante/patologia
Líquido da Lavagem Broncoalveolar/química
Linfócitos T CD8-Positivos/imunologia
Feminino
Seres Humanos
Células Matadoras Naturais/imunologia
Contagem de Linfócitos
Masculino
Meia-Idade
Período Pós-Operatório
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
126465-35-8 (Perforin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001592


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[PMID]:28863861
[Au] Autor:Palterer B; Brugnolo F; Sieni E; Barilaro A; Parronchi P
[Ad] Endereço:Department of Clinical and Experimental Medicine, Unit of Internal Medicine, University of Florence, Italy. Electronic address: boaz.palterer@unifi.it.
[Ti] Título:Neuromyelitis optica, atypical hemophagocytic lymphohistiocytosis and heterozygous perforin A91V mutation.
[So] Source:J Neuroimmunol;311:10-13, 2017 Oct 15.
[Is] ISSN:1872-8421
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Neuromyelitis optica is an autoimmune demyelinating inflammatory disease characterized by optic neuritis and myelitis with anti-aquaporin 4 antibodies. Hemophagocytic lymphohistiocytosis is a severe systemic inflammatory syndrome that can present in a genetic primary form or secondarily to infective, neoplastic or autoimmune diseases. Our case discusses the first reported case of atypical late-onset hemophagocytic lymphohistiocytosis in a patient with neuromyelitis optica, with multiple triggering factors and carrying the common A91V hypomorphic perforin mutation, that blurs the distinction between primary and secondary forms.
[Mh] Termos MeSH primário: Linfo-Histiocitose Hemofagocítica/genética
Mutação/genética
Neuromielite Óptica/genética
Perforina/genética
[Mh] Termos MeSH secundário: Corticosteroides/uso terapêutico
Alanina/genética
Antígenos CD/metabolismo
Seres Humanos
Linfócitos/efeitos dos fármacos
Linfócitos/patologia
Linfo-Histiocitose Hemofagocítica/complicações
Linfo-Histiocitose Hemofagocítica/diagnóstico por imagem
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Neuromielite Óptica/complicações
Neuromielite Óptica/diagnóstico por imagem
Neuromielite Óptica/tratamento farmacológico
Medula Espinal/diagnóstico por imagem
Valina/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Antigens, CD); 126465-35-8 (Perforin); HG18B9YRS7 (Valine); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE


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[PMID]:28582670
[Au] Autor:Spicer JA; Miller CK; O'Connor PD; Jose J; Huttunen KM; Jaiswal JK; Denny WA; Akhlaghi H; Browne KA; Trapani JA
[Ad] Endereço:Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, A New Zealand Centre for Research Excellence, Auckland, New Zealand. Electronic address: j.sp
[Ti] Título:Substituted arylsulphonamides as inhibitors of perforin-mediated lysis.
[So] Source:Eur J Med Chem;137:139-155, 2017 Sep 08.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection.
[Mh] Termos MeSH primário: Perforina/antagonistas & inibidores
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga
Seres Humanos
Células Jurkat/efeitos dos fármacos
Células Jurkat/metabolismo
Células Matadoras Naturais/efeitos dos fármacos
Células Matadoras Naturais/metabolismo
Estrutura Molecular
Perforina/metabolismo
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sulfonamides); 126465-35-8 (Perforin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE


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[PMID]:28410483
[Au] Autor:Molloy CT; Andonian JS; Seltzer HM; Procario MC; Watson ME; Weinberg JB
[Ad] Endereço:Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
[Ti] Título:Contributions of CD8 T cells to the pathogenesis of mouse adenovirus type 1 respiratory infection.
[So] Source:Virology;507:64-74, 2017 Jul.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CD8 T cells are key components of the immune response to viruses, but their roles in the pathogenesis of adenovirus respiratory infection have not been characterized. We used mouse adenovirus type 1 (MAV-1) to define CD8 T cell contributions to the pathogenesis of adenovirus respiratory infection. CD8 T cell deficiency in ß2m mice had no effect on peak viral replication in lungs, but clearance of virus was delayed in ß2m mice. Virus-induced weight loss and increases in bronchoalveolar lavage fluid total protein, IFN-γ, TNF-α, IL-10, CCL2, and CCL5 concentrations were less in ß2m mice than in controls. CD8 T cell depletion had similar effects on virus clearance, weight loss, and inflammation. Deficiency of IFN-γ or perforin had no effect on viral replication or inflammation, but perforin-deficient mice were partially protected from weight loss. CD8 T cells promote MAV-1-induced pulmonary inflammation via a mechanism that is independent of direct antiviral effects.
[Mh] Termos MeSH primário: Infecções por Adenoviridae/veterinária
Linfócitos T CD8-Positivos/imunologia
Pulmão/imunologia
Mastadenovirus/fisiologia
Doenças dos Roedores/imunologia
[Mh] Termos MeSH secundário: Infecções por Adenoviridae/genética
Infecções por Adenoviridae/imunologia
Infecções por Adenoviridae/virologia
Animais
Feminino
Interferon gama/genética
Interferon gama/imunologia
Interleucina-10/genética
Interleucina-10/imunologia
Pulmão/virologia
Masculino
Mastadenovirus/genética
Mastadenovirus/isolamento & purificação
Camundongos
Camundongos Endogâmicos C57BL
Perforina/genética
Perforina/imunologia
Doenças dos Roedores/genética
Doenças dos Roedores/virologia
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
126465-35-8 (Perforin); 130068-27-8 (Interleukin-10); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170415
[St] Status:MEDLINE


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[PMID]:28378637
[Au] Autor:Yan H; Zhang P; Kong X; Hou X; Zhao L; Li T; Yuan X; Fu H
[Ad] Endereço:1 Department of Dermatology, The First People's Hospital of Jining City, Jining, China.
[Ti] Título:Primary Tr1 cells from metastatic melanoma eliminate tumor-promoting macrophages through granzyme B- and perforin-dependent mechanisms.
[So] Source:Tumour Biol;39(4):1010428317697554, 2017 Apr.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells. Tr1 cells were characterized by high interleukin 10 secretion and low Foxp3 expression and were enriched in the CD4 CD49b LAG-3 T-cell fraction. Macrophages derived from peripheral blood monocytes in the presence of modified melanoma-conditioned media demonstrated tumor-promoting capacity, exemplified by improving the proliferation of cocultured A375 malignant melanoma cells. But when primary Tr1 cells were present in the macrophage-A375 coculture, the growth of A375 cells was abrogated. The conventional CD25 Treg cells, however, were unable to inhibit macrophage-mediated increase in tumor cell growth. Further analyses showed that Tr1 cells did not directly eliminate A375 cells, but mediated the killing of tumor-promoting macrophages through the secretion of granzyme B and perforin. The tumor-infiltrating interleukin 10 Foxp3 CD4 T cells expressed very low levels of granzyme B and perforin, possibly suggested the downregulation of Tr1 cytotoxic capacity in melanoma tumors. Together, these data demonstrated an antitumor function of Tr1 cells through the elimination of tumor-promoting macrophages, which was not shared by conventional Tregs.
[Mh] Termos MeSH primário: Granzimas/metabolismo
Macrófagos/fisiologia
Melanoma/imunologia
Perforina/metabolismo
Linfócitos T Reguladores/imunologia
[Mh] Termos MeSH secundário: Células Cultivadas
Citotoxicidade Imunológica
Seres Humanos
Melanoma/metabolismo
Melanoma/patologia
Metástase Neoplásica
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
126465-35-8 (Perforin); EC 3.4.21.- (Granzymes)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170410
[Lr] Data última revisão:
170410
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170406
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317697554



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