Cytokine-induced expression of mRNAs for chemotactic factors in human synovial cells and fibroblasts.
In response to interleukin 1 or tumor necrosis factor, human synovial cells and fibroblasts expressed several genes encoding known chemotactic factors or related proteins. Transcripts for interleukin 8 (IL-8), gro/MGSA, pAT 464, IP-10, pAT 744 and Monocyte Chemotactic and Activating Factor (MCAF) accumulated rapidly in IL-1 and TNF-treated cells. The inhibition of protein synthesis led to the superinduction of IL-8 and gro/MGSA mRNAs in IL-1, but not in TNF-treated cells. Thus, IL-1 and TNF are likely to regulate the expression of these mRNAs by different mechanisms. Important cell-specific differences in mRNA accumulation characterized the expression of chemotactic factor genes. Moreover, only a subset of the same genes was activated in quiescent cells stimulated by serum. Therefore, genes encoding closely related proteins each had a distinct pattern of expression. continuous stimulation of fibroblasts and synovial cells with IL-1 resulted in high and prolonged expression of IL-8 and gro/MGSA mRNAs. These results extend the list of chemotactic factor genes expressed by mesenchymal cells in vitro and suggest a pivotal role for these cells in processes such as chronic inflammation.
Bédard
P A
PA
Département de biochimie, Université de Montréal, Québec, Canada.
Golds
E E
EE
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000502:physiology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D005810:Multigene Family; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D013582:Synovial Fluid / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha