title: Hepatitis B virus X protein modulates renal tubular epithelial cell-induced T-cell and macrophage responses.
abstract: Renal tubular epithelial cells (RTECs) have an active role in renal inflammation, functioning as antigen-presenting cells as they constitutively express major histocompatibility complex-II and co-stimulatory molecules that can activate T cells and macrophages. Previous studies indicate that inflammatory cell infiltration and tubulointerstitial fibrosis are present in renal biopsies from Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) patients. We hypothesized that disorder RTECs may be involved in the progression of HBV-GN. Here, we measured renal function and inflammatory cells infiltration in C57BL/6J-TgN mice, and data showed that in C57BL/6J-TgN mice HBV x protein (HBx) mainly deposited in RTECs, and CD4(+) T cells and macrophages infiltrated into the interstitium. In vitro HBx upregulated CD40 expression in RTECs. In HK-2/CD4(+) T cells co-culture system, we found that HBx-stimulated HK-2 cells could activate CD4(+) T cells, promote their proliferation, and lead to an imbalance of interleukin (IL)-4 and interferon-γ. In HK-2/macrophages co-culture system, we found that HBx-stimulated HK-2 cells also increased macrophage adherent capacity and promoted MCP-1 and tumor necrosis factor-α and IL-1β secretion. These immune dysfunction may contribute to the pathogenesis of HBV-GN.
authors.affiliation: Department of Nephrology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Gu
authors.affiliation: Department of Nephrology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Yuan
mesh_terms: D000818:Animals; D015415:Biomarkers; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015415:Biomarkers; D019013:CD40 Antigens; D016207:Cytokines; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein