INDUCTION OF INTERLEUKIN (IL)-1-ALPHA AND BETA-GENE EXPRESSION IN HUMAN KERATINOCYTES EXPOSED TO REPETITIVE STRAIN - THEIR ROLE IN STRAIN-INDUCED KERATINOCYTE PROLIFERATION AND MORPHOLOGICAL CHANGE

Recent studies in our laboratory have demonstrated that mechanical str ain alters many facets of keratinocyte biology including proliferation , protein synthesis, and morphology. IL-1 is known to play an importan t role in the autocrine regulation of these basic cellular properties under basal and stimulated conditions. However, it is not known whethe r IL-l plays a role in strain-induced alteration of keratinocyte biolo gy. Thus, the objective of th is study was to test the hypothesis that cyclic strain stimulates IL-l expression and that strain-induced chan ges in keratinocyte function is regulated by IL-l. To test this hypoth esis, we examined the effect of cyclic strain (10% average deformation ) on keratinocyte IL-l gene expression and the effect of neutralizing antibodies of IL-1 alpha and IL-1 beta on strain-induced changes in ke ratinocyte proliferation, morphology, and orientation. Northern blot a nalyses demonstrated that steady state levels of IL-1 alpha and beta m RNA were elevated by 4 h, peaked at 12 h of cyclic strain (IL-1 alpha, 304 +/- 14.2%; IL-1 beta, 212 +/- 5.6% increase vs. static controls) and decreased gradually by 24 h. IL-1 antibodies (IL-1 alpha, 0.01 mu g/ml; IL-1 beta, 0.01 mu g/ml) significantly blocked strain-induced ke ratinocyte proliferation as well as the basal rate of proliferation. I n contrast, IL-1 antibodies (IL-1 alpha, 0.01 mu g/ml; IL-1 beta, 0.1 mu g/ml) had no effect on strain-induced morphological changes such as elongation and alignment. We conclude that mechanical strain induces IL-l mRNA expression in keratinocytes. The role of IL-1 in mediating s train-induced changes in keratinocyte biology remains to be determined but appears to be independent of morphological changes. (C) 1998 Wile y-Liss, Inc.