MODULATION OF MYCOPLASMA ARTHRITIDIS-DERIVED SUPERANTIGEN-INDUCED CYTOKINE GENE-EXPRESSION BY DEXAMETHASONE AND INTERLEUKIN-4

Activation of human monocytes or monocytic cell lines with all known s timuli coordinately induces the gene expression of various cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and the IL-1 receptor antagonist (IL-1Ra). In contrast, s uperantigens induce TNF-alpha and IL-1 beta but fail to affect IL-1Ra gene expression, suggesting that activation of monocytes via major his tocompatibility complex class II is distinct from other signal transdu ction pathways. In the present study, we analyzed the regulation of th e Mycoplasma arthritidis-derived superantigen (MAM)-induced IL-1 beta and TNF-alpha gene expression by studying the effects of two different anti-inflammatory agents: dexamethasone (DEX) and the T-cell-derived cytokine IL-4. Both agents contributed to the downregulation of MAM-in duced IL-1 beta and TNF-alpha gene expression. They accelerated the no rmal decline of the gene expression of both MAM induced cytokines by d ecreasing the stability of mRNAs via the induction or enhanced synthes is of one or more regulatory proteins. In addition, IL-4, but not DEX, induced a strong and rapid expression of IL-1Ra mRNA in MAM-stimulate d and unstimulated THP-1 cells in a de novo protein synthesis-independ ent manner. The capacity of IL-4 to induce IL-1Ra gene expression rein forces its anti-inflammatory activity. This study illustrates some of the mechanisms by which MAM-induced proinflammatory monokine gene expr ession can be downregulated by IL-4 and DEX.