Abstract
Inflammation in the joint of rheumatoid arthritis is a complex immune reaction facilitated by various factors, such as cytokines, cells and hypoxia. Thus, we evaluated their relative capacity to produce proinflammatory mediators in response to IL-1β, TNF-α or IL-17 under hypoxia or normoxia in fibroblast-like synoviocytes (FLSs) and macrophages. The level of IL-6 expression was strongly increased in both FLSs and THP-1 macrophages in response to IL-1β and TNF-α, but the level by TNF-α was less than that by IL-1β. In contrast, the expression of IL-8 in both cell types was strongly stimulated by both IL-1β and TNF-α. In FLSs, PGE2 production increased only in response to IL-1β; and no effect was observed in THP-1 cells and TNF-α-stimulated FLSs. In addition, the production by IL-17 was extremely low when compared with those induced by IL-1β or TNF-α in FLSs and THP-1 cells. Hypoxia (2% O2) decreased IL-1β-stimulated production of PGE2, even though it increased the expression of mRNA and protein of COX-2. These results suggest that IL-1β and TNF-α differentially regulate gene expression in FLSs and macrophages under hypoxia or normoxia.
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Maruotti N, Cantatore FP, Crivellato E, Vacca A, Ribatti D (2007) Macrophages in rheumatoid arthritis. Histol Histopathol 22:581–586
Pap T, Muller-Ladner U, Gay RE, Gay S (2000) Fibroblast biology: role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis. Arthritis Res 2:361–367
Mor A, Abramson SB, Pillinger MH (2005) The fibroblast-like synovial cell in rheumatoid arthritis: a key player in inflammation and joint destruction. Clin Immunol 115:118–128
Bromley M, Woolley DE (1984) Histopathology of the rheumatoid lesion. Identification of cell types at sites of cartilage erosion. Arthritis Rheum 27:857–863
Mulherin D, Fitzgerald O, Bresnihan B (1996) Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum 39:115–124
Demaziere A (1993) Macrophages in rheumatoid synovial membrane: an update. Rev Rheum Ed Fr 60:568–579
Yanni G, Whelan A, Feighery C, Bresnihan B (1994) Synovial tissue macrophages and joint erosion in rheumatoid arthritis. Ann Rheum Dis 53:39–44
Martel-Pelletier J, Pelletier JP, Fahmi H (2003) Cyclooxygenase-2 and prostaglandins in articular tissues. Semin Arthritis Rheum 33:155–167
van den Berg WB, Joosten LA, van de Loo FA (1999) TNF alpha and IL-1 beta are separate targets in chronic arthritis. Clin Exp Rheumatol 17:105–114
Feldmann M, Maini RN (1999) The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 38(Suppl 2):3–7
Feldmann M, Brennan FM, Maini RN (1996) Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14:397–440
Paleolog E (2003) The therapeutic potential of TNF-alpha blockade in rheumatoid arthritis. Expert Opin Investig Drugs 12:1087–1095
Mikuls TR, Moreland LW (2001) TNF blockade in the treatment of rheumatoid arthritis: infliximab versus etanercept. Expert Opin Pharmacother 2:75–84
Joosten LA, Helsen MM, Saxne T, van De Loo FA, Heinegard D, van Den Berg WB (1999) IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation. J Immunol 163:5049–5055
Fan PT, Leong KH (2007) The use of biological agents in the treatment of rheumatoid arthritis. Ann Acad Med Singap 36:128–134
Karouzakis E, Neidhart M, Gay RE, Gay S (2006) Molecular and cellular basis of rheumatoid joint destruction. Immunol Lett 106:8–13
Conti P, Youinou P, Theoharides TC (2007) Modulation of autoimmunity by the latest interleukins (with special emphasis on IL-32). Autoimmun Rev 6:131–137
Lund-Olesen K (1970) Oxygen tension in synovial fluids. Arthritis Rheum 13:769–776
Treuhaft PS, McCarty DJ (1971) Synovial fluid pH, lactate, oxygen and carbon dioxide partial pressure in various joint diseases. Arthritis Rheum 14:475–484
Berse B, Hunt JA, Diegel RJ, Morganelli P, Yeo K, Brown F, Fava RA (1999) Hypoxia augments cytokine (transforming growth factor-beta (TGF-beta) and IL-1)-induced vascular endothelial growth factor secretion by human synovial fibroblasts. Clin Exp Immunol 115:176–182
Sanchez-Elsner T, Botella LM, Velasco B, Corbi A, Attisano L, Bernabeu C (2001) Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression. J Biol Chem 276:38527–38535
Kim KS, Park EK, Ju SM, Jung HS, Bang JS, Kim C, Lee YA, Hong SJ, Lee SH, Yang HI, Yoo MC (2007) Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1beta stimulated fibroblast-like synoviocytes. Arthritis Res Ther 9:R80
Park EK, Jung HS, Yang HI, Yoo MC, Kim C, Kim KS (2007) Optimized THP-1 differentiation is required for the detection of responses to weak stimuli. Inflamm Res 56:45–50
Ahn JK, Koh EM, Cha HS, Lee YS, Kim J, Bae EK, Ahn KS (2008) Role of hypoxia-inducible factor-1alpha in hypoxia-induced expressions of IL-8, MMP-1 and MMP-3 in rheumatoid fibroblast-like synoviocytes. Rheumatology (Oxford) 47:834–839
Losa Garcia JE, Rodriguez FM, Martin de Cabo MR, Garcia Salgado MJ, Losada JP, Villaron LG, Lopez AJ, Arellano JL (1999) Evaluation of inflammatory cytokine secretion by human alveolar macrophages. Mediat Inflamm 8:43–51
Yoshida S, Katoh T, Tetsuka T, Uno K, Matsui N, Okamoto T (1999) Involvement of thioredoxin in rheumatoid arthritis: its costimulatory roles in the TNF-alpha-induced production of IL-6 and IL-8 from cultured synovial fibroblasts. J Immunol 163:351–358
Georganas C, Liu H, Perlman H, Hoffmann A, Thimmapaya B, Pope RM (2000) Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: the dominant role for NF-kappa B but not C/EBP beta or c-Jun. J Immunol 165:7199–7206
Gabay C (2006) Interleukin-6 and chronic inflammation. Arthritis Res Ther 8(Suppl 2):S3
Jackson C, Nguyen M, Arkell J, Sambrook P (2001) Selective matrix metalloproteinase (MMP) inhibition in rheumatoid arthritis—targeting gelatinase A activation. Inflamm Res 50:183–186
Malfait AM, Verbruggen G, Veys EM, Lambert J, De Ridder L, Cornelissen M (1994) Comparative and combined effects of interleukin 6, interleukin 1 beta, and tumor necrosis factor alpha on proteoglycan metabolism of human articular chondrocytes cultured in agarose. J Rheumatol 21:314–320
Stamp LK, Cleland LG, James MJ (2004) Upregulation of synoviocyte COX-2 through interactions with T lymphocytes: role of interleukin 17 and tumor necrosis factor-alpha. J Rheumatol 31:1246–1254
Suzuki M, Tetsuka T, Yoshida S, Watanabe N, Kobayashi M, Matsui N, Okamoto T (2000) The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-alpha- or IL-1beta-stimulated rheumatoid synovial fibroblasts. FEBS Lett 465:23–27
Kim KS, Rajagopal V, Gonsalves C, Johnson C, Kalra VK (2006) A novel role of hypoxia-inducible factor in cobalt chloride- and hypoxia-mediated expression of IL-8 chemokine in human endothelial cells. J Immunol 177:7211–7224
Kenneth NS, Rocha S (2008) Regulation of gene expression by hypoxia. Biochem J 414:19–29
Koritzinsky M, Magagnin MG, van den Beucken T, Seigneuric R, Savelkouls K, Dostie J, Pyronnet S, Kaufman RJ, Weppler SA, Voncken JW, Lambin P, Koumenis C, Sonenberg N, Wouters BG (2006) Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control. EMBO J 25:1114–1125
van den Beucken T, Koritzinsky M, Wouters BG (2006) Translational control of gene expression during hypoxia. Cancer Biol Ther 5:749–755
O’Dwyer PJ, Yao KS, Ford P, Godwin AK, Clayton M (1994) Effects of hypoxia on detoxicating enzyme activity and expression in HT29 colon adenocarcinoma cells. Cancer Res 54:3082–3087
Demasi M, Cleland LG, Cook-Johnson RJ, Caughey GE, James MJ (2003) Effects of hypoxia on monocyte inflammatory mediator production: dissociation between changes in cyclooxygenase-2 expression and eicosanoid synthesis. J Biol Chem 278:38607–38616
Demasi M, Cleland LG, Cook-Johnson RJ, James MJ (2004) Effects of hypoxia on the expression and activity of cyclooxygenase 2 in fibroblast-like synoviocytes: interactions with monocyte-derived soluble mediators. Arthritis Rheum 50:2441–2449
Kohro T, Tanaka T, Murakami T, Wada Y, Aburatani H, Hamakubo T, Kodama T (2004) A comparison of differences in the gene expression profiles of phorbol 12-myristate 13-acetate differentiated THP-1 cells and human monocyte-derived macrophage. J Atheroscler Thromb 11:88–97
Granet C, Miossec P (2004) Combination of the pro-inflammatory cytokines IL-1, TNF-alpha and IL-17 leads to enhanced expression and additional recruitment of AP-1 family members, Egr-1 and NF-kappaB in osteoblast-like cells. Cytokine 26:169–177
Lotito AP, Silva CA, Mello SB (2007) Interleukin-18 in chronic joint diseases. Autoimmun Rev 6:253–256
Chi JT, Wang Z, Nuyten DS, Rodriguez EH, Schaner ME, Salim A, Wang Y, Kristensen GB, Helland A, Borresen-Dale AL, Giaccia A, Longaker MT, Hastie T, Yang GP, van de Vijver MJ, Brown PO (2006) Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers. PLoS Med 3:e47
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This work was supported by a research grant from the Korean Ministry of Health and Welfare (03-PJ9-PG6-SO01-002).
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H. M. Choi and D. H. Oh contributed equally to this work.
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Choi, H.M., Oh, D.H., Bang, J.S. et al. Differential effect of IL-1β and TNF-α on the production of IL-6, IL-8 and PGE2 in fibroblast-like synoviocytes and THP-1 macrophages. Rheumatol Int 30, 1025–1033 (2010). https://doi.org/10.1007/s00296-009-1089-y
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DOI: https://doi.org/10.1007/s00296-009-1089-y