Differential effect of IL-1β and TNFα on the production of IL-6, IL-8 and PGE2 in fibroblast-like synoviocytes and THP-1 macrophages.
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-1beta, TNF-alpha 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-1beta and TNF-alpha, but the level by TNF-alpha was less than that by IL-1beta. In contrast, the expression of IL-8 in both cell types was strongly stimulated by both IL-1beta and TNF-alpha. In FLSs, PGE(2) production increased only in response to IL-1beta; and no effect was observed in THP-1 cells and TNF-alpha-stimulated FLSs. In addition, the production by IL-17 was extremely low when compared with those induced by IL-1beta or TNF-alpha in FLSs and THP-1 cells. Hypoxia (2% O(2)) decreased IL-1beta-stimulated production of PGE(2), even though it increased the expression of mRNA and protein of COX-2. These results suggest that IL-1beta and TNF-alpha differentially regulate gene expression in FLSs and macrophages under hypoxia or normoxia.
Choi
Hyun Mi
HM
East-West Neo Medical Center, East-West Bone and Joint Research Institute, Kyung Hee University, 149 Sangil-dong, Gangdong-gu, Seoul, Republic of Korea.
Oh
Da Hee
DH
Bang
Jun Soo
JS
Yang
Hyung-In
HI
Yoo
Myung Chul
MC
Kim
Kyoung Soo
KS
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone
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