RESUMO
PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin, a pore-forming toxin, is a common cause of necrotizing pneumonia. However, the early pulmonary inflammatory response following PVL(+) MRSA infection is unknown. The purpose of this study was to use a murine model to determine the effect of PVL(+) MRSA on lung tissues and the expression of cytokines and JAK and STAT mRNA and protein. METHODS: Mice were randomly divided into 3 groups and intra-nasally treated with PBS (control group), recombinant PVL (rPVL group), and PVL(+) MRSA (PVL group). At 24 and 48 h after inoculation, bronchoalveolar lavage fluid (BALF) was tested for cytokine levels, and lung tissues were tested for JAK and STAT mRNA and protein expression, and examined after hematoxylin and eosin staining. RESULTS: Mice infected with the PVL(+) strain became ill, characterized by impaired mobility, hunched posture, ruffled fur, and labored breathing. Lung tissue exhibited tissue necrosis and hemorrhage. BALF levels of IL-8, TNF-α, IFN-γ, IL-12, sICAM-1, and sVCAM-1 were increased in the rPVL or PVL groups, while levels of IL-10 and IL-4 levels were similar among the groups. JAK1 and STAT1 mRNA expression and protein levels were increased in lung tissue from mice infected with PVL(+) MRSA and rPVL. CONCLUSIONS: PVL is a significant S. aureus virulence factor, and upregulates the expression of proinflammatory cytokines but does not affect the expression of anti-inflammatory cytokines. The effect of PVL may be due to JAK/STAT pathway activation. Blockade of the JAK/STAT pathway may decrease the severity of PVL(+) MRSA pneumonia.
Assuntos
Toxinas Bacterianas/genética , Exotoxinas/genética , Leucocidinas/genética , Pneumonia Necrosante/metabolismo , Pneumonia Necrosante/microbiologia , Transdução de Sinais , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Toxinas Bacterianas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Exotoxinas/metabolismo , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Janus Quinases/metabolismo , Leucocidinas/metabolismo , Pneumonia Necrosante/genética , Fatores de Transcrição STAT/metabolismo , Infecções Estafilocócicas/genética , Staphylococcus aureus/imunologiaRESUMO
Ischemic stroke, gravely affecting human health with its increasing incidence rate , is a common disease of old age . JAK/STAT way , a recently discovered signaling pathway , is not only widely involved in processes of cell growth ,differentiation, and apoptosis ,but also closely related to the pathophysiology of stroke.However,the pathway function and mechanism in ische-mic cerebral stroke has not yet been fully elucidated .We will review the role and mechanism of JAK/STAT signal transduction pathway in ischemic stroke ,and scientifically draw network chart between various related signal molecules in the process of ische-mic stroke neuropathy combining both domestic and foreign re-search reported in this paper , in order to better understand the pathological mechanism process of brain stroke , find new drugs for the treatment of cerebral ischemic diseases ,then provide more systematic scientific literature support .
RESUMO
AIM: To investigate the effect of activation of JAK/STAT signaling pathway on the transdifferentiation induced by high concentration of glucose in renal proximal tubular epithelial cells(HKCs).METHODS: Cultured HKCs cells were divided into four groups: low glucose group(LG),high glucose group(HG),high mannitol group(LG+M),and HG+AG490 group(AG).Immunoprecipitation and Western blotting analysis were used to determine the expression of tryosine phosphorylated Janus kinase 2(p-JAK2).The protein expressions of STAT1,STAT3,p-STAT1 and p-STAT3 and expressions of ?-SMA,E-cadherin were observed by Western blotting.The contents of TGF-?1 and type I collagen in the supernatants of the cultured HKCs were detected by enzyme-linked immunoadsorbent assay(ELISA).TGF-?1 mRNA were measured by reverse transcription and polymerase chain reaction(RT-PCR).RESULTS: Compared with low glucose control group,the expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA was significantly increased in HG group at different stimulated time from 6 h to 72 h.Meanwhile,the contents of TGF-?1 and collagen I in the supernatants and the expression of ?-SMA were increased,the expression of E-cadherin were decreased.The expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA and the levels of TGF-?1,collagen I in the supernatants in HG+AG490 group were obviously lower than those in HG group.The expressions of ?-SMA and E-cadherin were also decreased in HG+AG490 group.CONCLUSION: Activation of JAK/STAT signaling pathway may be involved in the high glucose-induced transdifferentiation and overproduction of TGF?1 and ECM proteins in HKCs.
