Il-1β and prostaglandins regulate integrin mRNA expression

The purpose of this study was to examine the effects of IL‐1β on integrin expression in MG‐63 human osteosarcoma cells. Human recombinant IL‐1β (rIL‐1β) produced significant increases in both α2‐ and α5‐subunit mRNA levels, as well as a smaller increase in αv‐subunit mRNA. In contrast, IL‐1β decreased α4‐subunit mRNA levels by approximately 30% relative to untreated controls. These findings suggest that human IL‐1β differentially regulates expression of integrins. When cultures were treated with both IL‐1β and the cyclooxygenase inhibitor, indomethacin, the expression of α2‐, α5‐, and αv‐subunit mRNA levels were dramatically increased relative to untreated controls; co‐treatment with 0.5 mM prostaglandin E2 (PGE2) partially reversed this effect. Indomethacin alone did not affect integrin mRNA levels. Treatment with IL‐1β or IL‐1β + indomethacin also induced significant changes in MG‐63 morphology (i.e., increased cell elongation) and increased the ability of cells to contract collagen gels. PGE2 reversed the above effects on cell morphology and gel contraction. These findings indicate that (a) IL‐1β differentially regulates the expression of integrins and (b) that PGE2, which is induced by IL‐1β, may provide a negative feedback loop which counteracts the stimulatory effect of IL‐1β on integrin gene expression. It is suggested that products of inflammation may affect cell behavior by differentially regulating the expression of various integrins.