Effects of interferon-? and tumor necrosis factor ? on the expression of the genes encoding aggrecan, biglycan, and decorin core proteins in cultured human chondrocytes

Abstract

These data demonstrate that 1) the expression of the core protein genes encoding the cartilage proteoglycans aggrecan, biglycan, and decorin is differentially regulated by IFN gamma and TNF alpha; 2) these effects are mediated by transcriptional and posttranscriptional mechanisms; and 3) the combination of the 2 cytokines causes a potent inhibitory effect on the expression of the genes for the core proteins of these 3 proteoglycans, which occurs largely at the transcriptional level. The inhibition of aggrecan, decorin, and biglycan core protein gene expression by the combination of IFN gamma and TNF alpha may contribute to the cartilage destruction that is characteristic of inflammatory joint diseases.

Tumor necrosis factor ?-dependent proinflammatory gene induction is inhibited by cyclic tensile strain in articular chondrocytes in vitro

“…Our observations provide evidence that signals generated by CTS act as powerful antagonists of the actions of TNF␣, one of the proinflammatory cytokines implicated in the etiology of rheumatic diseases (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Interestingly, the observations that continuous passive motion reduces inflammation and facilitates physiologically sound recovery in orthopedic patients also point to the possible antiinflammatory/reparative actions of mechanical strain in vivo (15)(16)(17)(18)(19)(20).…”

“…Furthermore, in addition to stimulating cartilage degradation, TNF␣ inhibits synthesis of aggrecan and type II collagen (CII) (13,14). Collectively, induction of catabolic enzymes and inhibition of matrix synthesis by TNF␣ and IL-1␤ drive cartilage destruction in chronic inflammatory diseases such as RA or OA (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

An IFN-γ-Independent Proinflammatory Role of IL-18 in Murine Streptococcal Cell Wall Arthritis

“…Cytokine-induced NO synthesis by macrophages, synoviocytes, and chondrocytes is strongly enhanced by IFN-␥. Furthermore, synergistic effects on inhibition of chondrocyte PG synthesis between IL-1 and several other cytokines, such as TNF-␣ and IFN-␥, were demonstrated (39,40).…”

A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen α2(I) and Other Promoters

“…There are several examples of IFN-␥-suppressible promoters or genes, and these can be loosely grouped as the following: genes important for cell proliferation and cell differentiation, such as cyclin (51) and c-myc and N-myc (59); certain cytokine genes expressed by the TH2 subpopulation, such as interleukin 4 (IL-4) (15) and IL-10 (17); and genes coding for matrix proteins, such as the collagen (26,29,58) and proteoglycan (16,50) genes. The mechanism by which IFN-␥ causes gene suppression is not well known, and the present study shows that one mechanism involves the CIITA molecule.…”