title: C5a Induces the Synthesis of IL-6 and TNF-α in Rat Glomerular Mesangial Cells through MAPK Signaling Pathways.
abstract: Inflammatory response has been reported to contribute to the renal lesions in rat Thy-1 nephritis (Thy-1N) as an animal model of human mesangioproliferative glomerulonephritis (MsPGN). Besides C5b-9 complex, C5a is also a potent pro-inflammatory mediator and correlated to severity of various nephritic diseases. However, the role of C5a in mediating pro-inflammatory cytokine production in rats with Thy-1N is poorly defined. In the present studies, the levels of C5a, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were first determined in the renal tissues of rats with Thy-1N. Then, the expression of IL-6 and TNF-α was detected in rat glomerular mesangial cells (GMC) stimulated with our recombinant rat C5a in vitro. Subsequently, the activation of mitogen-activated protein kinase (MAPK) signaling pathways (p38 MAPK, ERK1/2 and JNK) and their roles in the regulation of IL-6 and TNF-α production were examined in the GMC induced by C5a. The results showed that the levels of C5a, IL-6 and TNF-α were markedly increased in the renal tissues of Thy-1N rats. Rat C5a stimulation in vitro could up-regulate the expression of IL-6 and TNF-α in rat GMC, and the activation of MAPK signaling pathways was involved in the induction of IL-6 and TNF-α. Mechanically, p38 MAPK activation promoted IL-6 production, while either ERK1/2 or JNK activation promoted TNF-α production in the GMC with exposure to C5a. Taken together, these data implicate that C5a induces the synthesis of IL-6 and TNF-α in rat GMC through the activation of MAPK signaling pathways.
authors: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.|Department of Laboratory Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, 210029, P.R. China.
authors: Mingde
authors: M
authors: Ji
authors: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.
authors: Yanlai
authors: Y
authors: Lu
authors: Department of Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P.R. China.
authors: Chenhui
authors: C
authors: Zhao
authors: Basic Medical Science of Basic Medical College, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.
authors: Wenxing
authors: W
authors: Gao
authors: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.
authors: Fengxia
authors: F
authors: He
authors: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.
authors: Jing
authors: J
authors: Zhang
authors: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.
authors: Dan
authors: D
authors: Zhao
authors: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.
authors: Wen
authors: W
authors: Qiu
authors: Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.
authors: Yingwei
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D015936:Complement C5a / Q000502:physiology*; D005920:Glomerular Mesangium / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D051381:Rats; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D044087:Receptor, Anaphylatoxin C5a; D014409:Tumor Necrosis Factor-alpha; D015936:Complement C5a