Autocrine stimulation of interleukin 1 in human adherent synovial lining cells: down regulation by interferon gamma.
Interleukin 1 (IL-1) exerts biological properties on various immune and nonimmune cell types and tissues and thus may play an important role during chronic inflammatory processes. Here we have examined the IL-1 biosynthesis in adherent synovial lining cell (ASLC) cultures obtained from patients with rheumatoid arthritis (RA). We report that ASLCs in culture showed heterogeneous endogenous levels of IL-1 alpha and beta expression. Recombinant interleukin 1 (rIL-1) alpha or beta induced increases of IL-1 alpha and beta mRNA and proteins levels in ASLCs. Although IL-1 synthesis is enhanced by rIL-1 treatment, no soluble IL-1 alpha or beta could be detected by specific enzyme-linked immunosorbent assays. A pretreatment with recombinant IFN gamma (rIFN gamma) down-regulated the effect of rIL-1 on IL-1 synthesis in ASLCs. Actinomycin D suppressed the endogeneous and rIL-1-induced IL-1 mRNA expression Indomethacin, in the presence of rIL-1 alpha or beta, up-regulates the level of expression of IL-1 beta in ASLCs pretreated with rIFN gamma, but has the opposite effect in non-pretreated cells. The increase of IL-1 gene expression by rIL-1 in human ASLCs from RA patients may contribute as an amplification of the disease progress. These studies may also explain the beneficial effects of IFN gamma in experimental models of IL-1-induced bone and cartilage degradation and in patients with diseases involving IL-1.
Temime
N
N
Laboratoire d'Immunogénétique Moléculaire, Institut Biomédical des Cordeliers, Paris, France.
Joliviere
A
A
Lando
D
D
Teyton
L
L
Charron
D
D
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013583:Synovial Membrane / Q000166:cytology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007213:Indomethacin