Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) mediates p38 mitogen-activated protein kinase activation and signal transduction in peripheral blood mononuclear cells from patients with lupus nephritis.
Forty-two patients with systemic lupus erythematosus (SLE), including 26 patients with renal damage and 16 without, and 20 healthy controls were included in the study. The isolated peripheral blood mononuclear cells (PBMCs) were treated with a p38 inhibitor (SB203580) or anti-tumor necrosis factor-like weak inducer of apoptosis (TWEAK) mAb, with or without phytohemagglutinin/phorbol myristate acetate (PHA/PMA) stimulation. Western blot experiments were used to evaluate the protein expression of TWEAK and p38 MAPK in PBMCs .Next, the contents of interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in the supernatant were measured by ELISA. The results showed that expression of TWEAK protein in PBMCs from lupus nephritis patients was significantly higher than that from SLE patients without renal damage and healthy controls. PHA/PMA simulation could upregulate the productions of TWEAK and p-p38MAPK in PBMCs from patients with SLE. Anti-TWEAK mAb treatment downregulated both TWEAK and p-p38 MAPK expression in PBMCs, as well as IL-10 and MCP-1 in the supernatant; SB203580 had the same effect on cytokine production in PBMC, but had no effect on the expression of TWEAK. Our results suggested that TWEAK-p38 MAPK-IL-10, MCP-1 signaling pathway in PBMC played an important pathogenic role in lupus nephritis.
Department of Rheumatology and Immunology, The Second Affiliated Hospital of Suzhou University, Suzhou, China.
Liu
L
Zhi-Chun
Zhou
Z
Qiao-Ling
Liu
L
Zhi-Qin
Li
L
Xiao-Zhao
Zuo
Z
Xiao-xia
Tang
T
Rong
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism*; D000074050:TWEAK Receptor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D048069:Tumor Necrosis Factors / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007093:Imidazoles; D010835:Phytohemagglutinins; D011725:Pyridines; D018124:Receptors, Tumor Necrosis Factor; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C093642:SB 203580