Synergistic effect of pro-inflammatory TNFα and IL-17 in periostin mediated collagen deposition: Potential role in liver fibrosis
| Autor: | Venkataswarup Tiriveedhi, Kevin L. Schey, Sade-Kemi Brown, Babak Banan, Margaret M. Whalen, Suneetha Amara, Michael T. Ivy, Karina Lopez, Elbert L. Myles, Terrance Johnson |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Liver Cirrhosis
STAT3 Transcription Factor Transcription Genetic Proto-Oncogene Proteins c-jun Immunology Periostin Biology Article Collagen Type I Proinflammatory cytokine Western blot Fibrosis medicine Humans Promoter Regions Genetic Molecular Biology Transcription factor medicine.diagnostic_test Tumor Necrosis Factor-alpha Interleukin-17 Interleukin DNA Neoplasm Hep G2 Cells Fibroblasts medicine.disease Molecular biology Cancer research Tumor necrosis factor alpha Inflammation Mediators Cell Adhesion Molecules Type I collagen Protein Binding |
| Popis: | The pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-17, have been implicated in the pathogenesis of liver fibrosis. In this study, we investigated the role of TNFα and IL-17 toward induction of profibrotic factor, periostin.HepG2 cells were cultured and treated with inflammatory cytokines, TNFα and IL-17. Computational promoter sequence analysis of the periostin promoter was performed to define the putative binding sites for transcription factors. Transcription factors were analyzed by Western blot and Chromatin Immunoprecipitation. Periostin and transcription factor expression analysis was performed by RT-PCR, Western blot, and fluorescence microscopy. Type I collagen expression from fibroblast cultures was analyzed by Western blot and Sircol soluble collagen assay.Activation of HepG2 Cells with TNFα and IL-17 enhanced the expression of periostin (3.5 and 4.4 fold, respectively p0.05) compared to untreated cells. However, combined treatment with both TNFα and IL-17 at similar concentration demonstrated a 13.3 fold increase in periostin (p0.01), thus suggesting a synergistic role of these cytokines. Periostin promoter analysis and specific siRNA knock-down revealed that TNFα induces periostin through cJun, while IL-17 induced periostin via STAT-3 signaling mechanisms. Treatment of the supernatant from the cytokine activated HepG2 cells on fibroblast cultures induced enhanced expression of type I collagen (9.1 fold, p0.01), indicative of a direct fibrogenic effect of TNFα and IL-17.TNFα and IL-17 induced fibrogenesis through cJun and STAT-3 mediated expression of profibrotic biomarker, periostin. Therefore, periostin might serve as a novel biomarker in early diagnosis of liver fibrosis. |
| Databáze: | OpenAIRE |
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