IL-29 Enhances LPS/TLR4-Mediated Inflammation in Rheumatoid Arthritis

• Published in: Cellular physiology and biochemistry Vol. 37; no. 1; pp. 27 - 34
• Main Authors: Xu, Donghua, Yan, Shushan, Wang, Huijuan, Gu, Bingjie, Sun, Keyi, Yang, Xiaofan, Sun, Bin, Wang, Xiaodong
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.01.2015
• Subjects: Animals; Arthritis, Rheumatoid - chemically induced; Arthritis, Rheumatoid - metabolism; Cell Line; Female; Humans; Inflammation - chemically induced; Inflammation - metabolism; Interferons; Interleukin-29; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Interleukins - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lipopolysaccharides - pharmacology; Male; Mice; Middle Aged; NF-kappa B - metabolism; Nuclear factor-κB; Original Paper; Rheumatology arthritis; Signal Transduction - drug effects; Synovial Fluid - metabolism; Toll-like receptor 4; Toll-Like Receptor 4 - metabolism; Tumor Necrosis Factor-alpha - metabolism; Rheumatology arthritis; Interleukin-29; Nuclear factor-κB; Toll-like receptor 4
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000430330

Background/Aims: Interleukin-29 (IL-29), a critical member of type III interferons (IFNs) family, has been implicated in protecting against viral infection and modulating autoimmune inflammation. Toll-like receptor 4 (TLR4) plays a crucial role in synovial inflammation and may contribute to the pathogenesis of rheumatology arthritis (RA). However, little is known about the modifying effect of IL-29 on TLR4-mediated inflammation in RA. We aim to investigate the potential association between IL-29 and TLR4 in RA. Methods: Peripheral blood mononuclear cells (PBMCs) and serum from 77 patients with RA and 70 controls were collected to determine levels of IL-29 and TLR4 mRNA by real-time polymerase chain reaction (PCR). Levels of IL-29 and TLR4 in synovial tissues and fluid from 25 RA patients and 24 controls were detected by enzyme-linked immunosorbent assay (ELISA) or western blot assay, respectively. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) and/or IL-29. The production of inflammatory cytokines including IL-6, IL-8 as well as TNF-a and the activation of nuclear factor-κB (NF-κB) signaling were determined. Results: In comparison with controls, increased IL-29 was observed in PBMCs, synovial tissue, serum and synovial fluid of patients with RA. Besides, TLR4 was significantly elevated in PBMCs and synovium of RA patients. Moreover, IL-29 was positively associated with TLR4 in RA, suggested by Pearson's correlation analysis. When RAW264.7 cells were stimulated by LPS with or without IL-29 in vitro, IL-29 could enhance LPS-mediated TLR4 expression and the production of IL-6, IL-8 and TNF-a in RAW264.7 cells via the activation of NF-κB signaling. Conclusion: The present study suggests, for the first time, that IL-29 can aggravate LPS/TLR4-mediated inflammation in RA depending on NF-κB signaling activation.