The online version of this article (doi:10.1186/ar3398) contains supplementary material, which is available to authorized users.
Yu-Jung Heo, Hye-Jwa Oh, Young Ok Jung, Mi-La Cho contributed equally to this work.
The authors declare that they have no competing interests.
YJH, YOJ, and MLC contributed to conception and design, acquisition of data, analysis and interpretation of data, drafting of the article and final approval of the submitted manuscript. OHJ, JGY and SYL contributed to immunohistochemistry. HRK, MKP and SHL helped with PCR, Western blotting and ELISA, and SHP and HYK contributed cell culture and transfection. All authors approved the final manuscript.
The receptor for advanced glycation end-products (RAGE) has been implicated in the pathogenesis of arthritis. We conducted this study to determine the effect of interleukin (IL)-17 on the expression and production of RAGE in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). The role of nuclear factor-κB (NF-κB) activator 1 (Act1) in IL-17-induced RAGE expression in RA-FLS was also evaluated.
RAGE expression in synovial tissues was assessed by immunohistochemical staining. RAGE mRNA production was determined by real-time polymerase chain reaction. Act-1 short hairpin RNA (shRNA) was produced and treated to evaluate the role of Act-1 on RAGE production.
RAGE, IL-17, and Act-1 expression increased in RA synovium compared to osteoarthritis synovium. RAGE expression and production increased by IL-17 and IL-1β (*P <0.05 vs. untreated cells) treatment but not by tumor necrosis factor (TNF)-α in RA-FLS. The combined stimuli of both IL-17 and IL-1β significantly increased RAGE production compared to a single stimulus with IL-17 or IL-1β alone (P <0.05 vs. 10 ng/ml IL-17). Act-1 shRNA added to the RA-FLS culture supernatant completely suppressed the enhanced production of RAGE induced by IL-17.
RAGE was overexpressed in RA synovial tissues, and RAGE production was stimulated by IL-17 and IL-1β. Act-1 contributed to the stimulatory effect of IL-17 on RAGE production, suggesting a possible inhibitory target for RA treatment.
Schmidt AM, Vianna M, Gerlach M, Brett J, Ryan J, Kao J, Esposito C, Hegarty H, Hurley W, Clauss M: Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J Biol Chem. 1992, 267: 14987-14997. PubMed
Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A: Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem. 1992, 267: 14998-15004. PubMed
Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM: RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell. 1999, 97: 889-901. 10.1016/S0092-8674(00)80801-6. CrossRefPubMed
Hudson BI, Bucciarelli LG, Wendt T, Sakaguchi T, Lalla E, Qu W, Lu Y, Lee L, Stern DM, Naka Y, Ramasamy R, Yan SD, Yan SF, D'Agati V, Schmidt AM: Blockade of receptor for advanced glycation endproducts: a new target for therapeutic intervention in diabetic complications and inflammatory disorders. Arch Biochem Biophys. 2003, 419: 80-88. 10.1016/j.abb.2003.08.030. CrossRefPubMed
Kokkola R, Sundberg E, Ulfgren AK, Palmblad K, Li J, Wang H, Ulloa L, Yang H, Yan XJ, Furie R, Chiorazzi N, Tracey KJ, Andersson U, Harris HE: High mobility group box chromosomal protein 1: a novel proinflammatory mediator in synovitis. Arthritis Rheum. 2002, 46: 2598-2603. 10.1002/art.10540. CrossRefPubMed
Chabaud M, Fossiez F, Taupin JL, Miossec P: Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol. 1998, 161: 409-414. PubMed
Crotti TN, Smith MD, Weedon H, Ahern MJ, Findlay DM, Kraan M, Tak PP, Haynes DR: Receptor activator NF-kappaB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis. Ann Rheum Dis. 2002, 61: 1047-1054. 10.1136/ard.61.12.1047. PubMedCentralCrossRefPubMed
Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, Kendall DA, Scammell BE, Reeve AJ, Chapman V: Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2008, 10: R43-10.1186/ar2401. PubMedCentralCrossRefPubMed
Steenvoorden MM, Huizinga TW, Verzijl N, Bank RA, Ronday HK, Luning HA, Lafeber FP, Toes RE, DeGroot J: Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes. Arthritis Rheum. 2006, 54: 253-263. 10.1002/art.21523. CrossRefPubMed
Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP: IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol. 1998, 160: 3513-3521. PubMed
Pickens SR, Volin MV, Mandelin AM, Kolls JK, Pope RM, Shahrara S: IL-17 contributes to angiogenesis in rheumatoid arthritis. J Immunol. 184: 3233-3241.
Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T: : IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999, 103: 1345-1352. 10.1172/JCI5703. PubMedCentralCrossRefPubMed
Arancio O, Zhang HP, Chen X, Lin C, Trinchese F, Puzzo D, Liu S, Hegde A, Yan SF, Stern A, Luddy JS, Lue LF, Walker DG, Roher A, Buttini M, Mucke L, Li W, Schmidt AM, Kindy M, Hyslop PA, Stern DM, Du Yan SS: RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO J. 2004, 23: 4096-4105. 10.1038/sj.emboj.7600415. PubMedCentralCrossRefPubMed
Lue LF, Walker DG, Brachova L, Beach TG, Rogers J, Schmidt AM, Stern DM, Yan SD: Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer's disease: identification of a cellular activation mechanism. Exp Neurol. 2001, 171: 29-45. 10.1006/exnr.2001.7732. CrossRefPubMed
- The expression of the receptor for advanced glycation end-products (RAGE) in RA-FLS is induced by IL-17 via Act-1
Young Ok Jung
- BioMed Central
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