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Rheumatology International

, Volume 30, Issue 8, pp 1025–1033 | Cite as

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

  • Hyun Mi Choi
  • Da Hee Oh
  • Jun Soo Bang
  • Hyung-In Yang
  • Myung Chul YooEmail author
  • Kyoung Soo KimEmail author
Original Article

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.

Keywords

Fibroblast-like synoviocyte Macrophage Rheumatoid arthritis COX-2 TNF-α IL-1β Hypoxia 

Notes

Acknowledgments

This work was supported by a research grant from the Korean Ministry of Health and Welfare (03-PJ9-PG6-SO01-002).

References

  1. 1.
    Maruotti N, Cantatore FP, Crivellato E, Vacca A, Ribatti D (2007) Macrophages in rheumatoid arthritis. Histol Histopathol 22:581–586PubMedGoogle Scholar
  2. 2.
    Pap T, Muller-Ladner U, Gay RE, Gay S (2000) Fibroblast biology: role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis. Arthritis Res 2:361–367CrossRefPubMedGoogle Scholar
  3. 3.
    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 115:118–128CrossRefPubMedGoogle Scholar
  4. 4.
    Bromley M, Woolley DE (1984) Histopathology of the rheumatoid lesion. Identification of cell types at sites of cartilage erosion. Arthritis Rheum 27:857–863CrossRefPubMedGoogle Scholar
  5. 5.
    Mulherin D, Fitzgerald O, Bresnihan B (1996) Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum 39:115–124CrossRefPubMedGoogle Scholar
  6. 6.
    Demaziere A (1993) Macrophages in rheumatoid synovial membrane: an update. Rev Rheum Ed Fr 60:568–579Google Scholar
  7. 7.
    Yanni G, Whelan A, Feighery C, Bresnihan B (1994) Synovial tissue macrophages and joint erosion in rheumatoid arthritis. Ann Rheum Dis 53:39–44CrossRefPubMedGoogle Scholar
  8. 8.
    Martel-Pelletier J, Pelletier JP, Fahmi H (2003) Cyclooxygenase-2 and prostaglandins in articular tissues. Semin Arthritis Rheum 33:155–167CrossRefPubMedGoogle Scholar
  9. 9.
    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 17:105–114Google Scholar
  10. 10.
    Feldmann M, Maini RN (1999) The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 38(Suppl 2):3–7Google Scholar
  11. 11.
    Feldmann M, Brennan FM, Maini RN (1996) Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14:397–440CrossRefPubMedGoogle Scholar
  12. 12.
    Paleolog E (2003) The therapeutic potential of TNF-alpha blockade in rheumatoid arthritis. Expert Opin Investig Drugs 12:1087–1095CrossRefPubMedGoogle Scholar
  13. 13.
    Mikuls TR, Moreland LW (2001) TNF blockade in the treatment of rheumatoid arthritis: infliximab versus etanercept. Expert Opin Pharmacother 2:75–84CrossRefPubMedGoogle Scholar
  14. 14.
    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 163:5049–5055PubMedGoogle Scholar
  15. 15.
    Fan PT, Leong KH (2007) The use of biological agents in the treatment of rheumatoid arthritis. Ann Acad Med Singap 36:128–134PubMedGoogle Scholar
  16. 16.
    Karouzakis E, Neidhart M, Gay RE, Gay S (2006) Molecular and cellular basis of rheumatoid joint destruction. Immunol Lett 106:8–13CrossRefPubMedGoogle Scholar
  17. 17.
    Conti P, Youinou P, Theoharides TC (2007) Modulation of autoimmunity by the latest interleukins (with special emphasis on IL-32). Autoimmun Rev 6:131–137CrossRefPubMedGoogle Scholar
  18. 18.
    Lund-Olesen K (1970) Oxygen tension in synovial fluids. Arthritis Rheum 13:769–776CrossRefPubMedGoogle Scholar
  19. 19.
    Treuhaft PS, McCarty DJ (1971) Synovial fluid pH, lactate, oxygen and carbon dioxide partial pressure in various joint diseases. Arthritis Rheum 14:475–484CrossRefPubMedGoogle Scholar
  20. 20.
    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 115:176–182CrossRefPubMedGoogle Scholar
  21. 21.
    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 276:38527–38535CrossRefPubMedGoogle Scholar
  22. 22.
    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:R80CrossRefPubMedGoogle Scholar
  23. 23.
    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 56:45–50CrossRefPubMedGoogle Scholar
  24. 24.
    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) 47:834–839CrossRefGoogle Scholar
  25. 25.
    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 8:43–51CrossRefGoogle Scholar
  26. 26.
    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 163:351–358PubMedGoogle Scholar
  27. 27.
    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 165:7199–7206PubMedGoogle Scholar
  28. 28.
    Gabay C (2006) Interleukin-6 and chronic inflammation. Arthritis Res Ther 8(Suppl 2):S3CrossRefPubMedGoogle Scholar
  29. 29.
    Jackson C, Nguyen M, Arkell J, Sambrook P (2001) Selective matrix metalloproteinase (MMP) inhibition in rheumatoid arthritis—targeting gelatinase A activation. Inflamm Res 50:183–186CrossRefPubMedGoogle Scholar
  30. 30.
    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 21:314–320PubMedGoogle Scholar
  31. 31.
    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 31:1246–1254PubMedGoogle Scholar
  32. 32.
    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 465:23–27CrossRefPubMedGoogle Scholar
  33. 33.
    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 177:7211–7224PubMedGoogle Scholar
  34. 34.
    Kenneth NS, Rocha S (2008) Regulation of gene expression by hypoxia. Biochem J 414:19–29CrossRefPubMedGoogle Scholar
  35. 35.
    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 25:1114–1125CrossRefPubMedGoogle Scholar
  36. 36.
    van den Beucken T, Koritzinsky M, Wouters BG (2006) Translational control of gene expression during hypoxia. Cancer Biol Ther 5:749–755PubMedGoogle Scholar
  37. 37.
    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 54:3082–3087PubMedGoogle Scholar
  38. 38.
    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 278:38607–38616CrossRefPubMedGoogle Scholar
  39. 39.
    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 50:2441–2449CrossRefPubMedGoogle Scholar
  40. 40.
    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 11:88–97PubMedGoogle Scholar
  41. 41.
    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 26:169–177CrossRefPubMedGoogle Scholar
  42. 42.
    Lotito AP, Silva CA, Mello SB (2007) Interleukin-18 in chronic joint diseases. Autoimmun Rev 6:253–256CrossRefPubMedGoogle Scholar
  43. 43.
    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:e47CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.East-West Neo Medical Center, East-West Bone and Joint Research InstituteKyung Hee UniversitySeoulRepublic of Korea
  2. 2.Department of Orthopedic Surgery, East-West Neo Medical CenterKyung Hee UniversitySeoulRepublic of Korea

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