IL-1 beta and prostaglandins regulate integrin mRNA expression.
The purpose of this study was to examine the effects of IL-1 beta on integrin expression in MG-63 human osteosarcoma cells. Human recombinant IL-1 beta (rIL-1 beta) produced significant increases in both alpha 2- and alpha 5-subunit mRNA levels, as well as a smaller increase in alpha v-subunit mRNA. In contrast, IL-1 beta decreased alpha 4-subunit mRNA levels by approximately 30% relative to untreated controls. These findings suggest that human IL-1 beta differentially regulates expression of integrins. When cultures were treated with both IL-1 beta and the cyclooxygenase inhibitor, indomethacin, the expression of alpha 2-, alpha 5-, and alpha 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-1 beta or IL-1 beta + 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-1 beta differentially regulates the expression of integrins and (b) that PGE2, which is induced by IL-1 beta, may provide a negative feedback loop which counteracts the stimulatory effect of IL-1 beta on integrin gene expression. It is suggested that products of inflammation may affect cell behavior by differentially regulating the expression of various integrins.
Milam
S B
SB
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
Magnuson
V L
VL
Steffensen
B
B
Chen
D
D
Klebe
R J
RJ
D000199:Actins / Q000235:genetics; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics*; D007375:Interleukin-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000199:Actins; D016023:Integrins; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003094:Collagen; D015232:Dinoprostone; D007213:Indomethacin