RESUMO
Basophils have often been erroneously considered to be minor relatives or blood-circulating precursors of tissue-resident mast cells because of some phenotypic similarity between them, including basophilic secretory granules in the cytoplasm. However, recent studies revealed that the repertoire of serine proteases stored in secretory granules is distinct in them. Particularly, mouse mast cell protease 8 (mMCP-8) is specifically expressed by basophils but not mast cells despite its name. Therefore, mMCP-8 is commonly used as a basophil-specific marker, but its functional property remains uncertain. Here we prepared recombinant mMCP-8 and examined its activity in vitro and in vivo Purified recombinant mMCP-8 showed heat-sensitive proteolytic activity when α-tubulin was used as a substrate. One intradermal shot of mMCP-8, not heat-inactivated, induced cutaneous swelling with increased microvascular permeability in a cyclooxygenase-dependent manner. Moreover, repeated intradermal injection of mMCP-8 promoted skin infiltration of leukocytes, predominantly neutrophils and, to a lesser extent, monocytes and eosinophils, in conjunction with up-regulation of chemokine expression in the skin lesion. These results suggest that mMCP-8 is an important effector molecule in basophil-elicited inflammation, providing novel insights into how basophils exert a crucial and non-redundant role, distinct from that played by mast cells, in immune responses.
Assuntos
Dermatite/enzimologia , Inflamação/enzimologia , Leucócitos/metabolismo , Mastócitos/enzimologia , Pele/metabolismo , Triptases/metabolismo , Animais , Dermatite/genética , Dermatite/patologia , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Leucócitos/patologia , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Pele/patologia , Triptases/genética , Triptases/toxicidade , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismoRESUMO
Interleukin (IL)-27, a member of the IL-6/IL-12 heterodimeric cytokine family, induces pro-inflammatory responses including early T helper (Th)1 differentiation and generation of cytotoxic T lymphocytes, and also anti-inflammatory responses including the differentiation to IL-10-producing regulatory T cells, inhibition of Th2 and Th17 differentiation, and suppression of pro-inflammatory cytokine production. Nitric oxide (NO) is a potent source of reactive nitrogen species that play an important role in killing intracellular pathogens and forms a crucial component of host defense. Inducible NO synthase (iNOS), which catalyzes the production of NO, is induced by a range of stimuli including cytokines and microbes. Recently, IL-27 was reported to play an anti-inflammatory role in microglia by blocking oncostatin M-induced iNOS expression and neuronal toxicity. In the present study, we investigated the effects of IL-27 on NO production in thioglycollate-elicited peritoneal macrophages. IL-27 together with lipopolysaccharide (LPS) induced morphological change into more spread and elongated cells and synergistically enhanced NO production. The combined stimulation also enhanced iNOS mRNA expression and the NO production was abrogated by an iNOS inhibitor, NG-monomethyl L-arginine. The synergistic NO production could be attributed to the augmented Toll-like receptor (TLR)4 mRNA expression by the combination. Signal transducer and activator of transcription (STAT)1 was indispensable for the morphological change and NO production. The combination induced nuclear factor κB (NF-κB) translocation into nuclear and phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and their inhibitors suppressed NO production. These results suggest that in contrast to the anti-proinflammatory role in microglia, IL-27 exerts a pro-inflammatory role by enhancing NO production in peritoneal macrophages stimulated with LPS through activation of STAT1, NF-κB and MAPKs.
Assuntos
MAP Quinases Reguladas por Sinal Extracelular/imunologia , Interleucinas/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/imunologia , NF-kappa B/imunologia , Óxido Nítrico/imunologia , Fator de Transcrição STAT1/imunologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/imunologia , Animais , Núcleo Celular/imunologia , Núcleo Celular/metabolismo , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/imunologia , Interleucinas/metabolismo , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/patologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/imunologia , Fator de Transcrição STAT1/metabolismo , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , ômega-N-Metilarginina/farmacologiaRESUMO
Th2-type inflammation spontaneously shown in Bcl6-knockout (KO) mice is mainly caused by bone marrow (BM)-derived nonlymphoid cells. However, the function of dendritic cells (DCs) in Bcl6-KO mice has not been reported. We show in this article that the numbers of CD4(+) conventional DCs (cDCs) and CD8α(+) cDCs, but not of plasmacytoid DCs, were markedly reduced in the spleen of Bcl6-KO mice. Generation of cDCs from DC progenitors in BM cells was perturbed in the spleen of irradiated wild-type (WT) mice transferred with Bcl6-KO BM cells, indicating an intrinsic effect of Bcl6 in cDC precursors. Although cDC precursors were developed in a Bcl6-KO BM culture with Fms-like tyrosine kinase 3 ligand, the cDC precursors were more apoptotic than WT ones. Also p53, one of the molecular targets of Bcl6, was overexpressed in the precursors. The addition of a p53 inhibitor to Bcl6-KO BM culture protected apoptosis, suggesting that Bcl6 is required by cDC precursors for survival by controlling p53 expression. Furthermore, large numbers of T1/ST2(+) Th2 cells were naturally developed in the spleen of Bcl6-KO mice. Th2 skewing was accelerated in the culture of WT CD4 T cells stimulated with Ags and LPS-activated Bcl6-KO BM-derived DCs, which produced more IL-6 and less IL-12 than did WT DCs; the addition of anti-IL-6 Abs to the culture partially abrogated the Th2 skewing. These results suggest that Bcl6 is required in cDC precursors for survival and in activated DCs for modulating the cytokine profile.
Assuntos
Antígenos CD4/biossíntese , Antígenos CD8/biossíntese , Diferenciação Celular/imunologia , Proteínas de Ligação a DNA/fisiologia , Células Dendríticas/imunologia , Animais , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Células da Medula Óssea/efeitos da radiação , Antígenos CD4/efeitos da radiação , Antígenos CD8/efeitos da radiação , Diferenciação Celular/genética , Diferenciação Celular/efeitos da radiação , Células Cultivadas , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/efeitos da radiação , Células Dendríticas/efeitos da radiação , Células Dendríticas/transplante , Linfopenia/genética , Linfopenia/imunologia , Linfopenia/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-bcl-6 , Baço/imunologia , Baço/patologia , Baço/efeitos da radiaçãoRESUMO
An 8-year-old female Persian cat was brought in for evaluation of chronic vomiting. The presence of opaque enteric foreign bodies and intestinal obstruction along with azotaemia, hyperphosphataemia, moderate anaemia and peritoneal fluid were revealed following appropriate diagnostic work-up. Exploratory laparotomy confirmed jejunoileal dilation, ileocaecal stenosis, and numerous foreign objects in the jejunoileum. These foreign objects and ileocaecal stenosis were surgically removed, and intestinal resection and anastomosis was performed. The patient recovered favourably. Analysis revealed that the foreign objects were composed of calcium phosphate and calcium carbonate. Intestinal inflammation and stenosis secondary to enterolithiasis may have developed following ingestion of cat litter or a previous unrelated surgical intervention. We were unable to delineate the inciting pathogenesis in this particular case.
Assuntos
Bezoares/veterinária , Doenças do Gato/cirurgia , Reação a Corpo Estranho/veterinária , Obstrução Intestinal/veterinária , Doenças do Jejuno/veterinária , Litíase/veterinária , Animais , Bezoares/complicações , Bezoares/cirurgia , Doenças do Gato/etiologia , Doenças do Gato/patologia , Gatos , Feminino , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/cirurgia , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Doenças do Jejuno/etiologia , Doenças do Jejuno/cirurgia , Laparotomia , Litíase/complicações , Litíase/cirurgiaRESUMO
After the Long-Term Care Insurance (LTCI) regulation has been enacted, all the daycare agencies/institutions must provide functional trainings to their clients as one of the standard services. However, the regulation is limited only to their personnel arrangement rather than the service content, which is left to each agency/institution. We feel that functional trainings as a daycare service need more attention so that we can bridge the content gaps between agencies/institutions. To solve this problem, we planned to send training professionals to these daycare providers in the surrounding areas. At the same time, we have been holding training courses for daycare staff and each trainer, which contributed to fill the knowledge and skill gaps between these trainers. The purpose of this paper is to report our study with some suggestions about the ideal functional trainings in the future daycare services.
Assuntos
Hospital Dia/normas , Capacitação em Serviço , Seguro de Assistência de Longo Prazo , Humanos , Avaliação das Necessidades , Apoio SocialRESUMO
After the Long-Term Care Insurance (LTCI) regulation has been enacted, all the daycare agencies/institutions must provide functional trainings to their clients as one of the standard services. However, the regulation is limited only to their personnel arrangement rather than the service content, which is left to each agency/institution. We feel that functional trainings as a daycare service need more attention so that we can bridge the content gaps between agencies/institutions. To solve this problem, we planned to send training professionals to these daycare providers in the surrounding areas. At the same time, we have been holding training courses for daycare stuff and each trainer, which contributed to fill the knowledge and skill gaps between these trainers'. The purpose of this paper is to report our study with some suggestions about the ideal functional trainings in the future daycare services.