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 α_v‐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 α_v‐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.