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 strain alters many facets of keratinocyte biology including proliferation, protein synthesis, and morphology. IL-1 is known to play an important role in the autocrine regulation of these basic cellular properties under basal and stimulated conditions. However, it is not known whether IL-1 plays a role in strain-induced alteration of keratinocyte biology. Thus, the objective of this study was to test the hypothesis that cyclic strain stimulates IL-1 expression and that strain-induced changes in keratinocyte function is regulated by IL-1. To test this hypothesis, we examined the effect of cyclic strain (10% average deformation) on keratinocyte IL-1 gene expression and the effect of neutralizing antibodies of IL-1 alpha and IL-1 beta on strain-induced changes in keratinocyte proliferation, morphology, and orientation. Northern blot analyses demonstrated that steady state levels of IL-1 alpha and beta mRNA were elevated by 4 h, peaked at 1 2 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 microg/ml; IL-1 beta, 0.01 microg/ml) significantly blocked strain-induced keratinocyte proliferation as well as the basal rate of proliferation. In contrast, IL-1 antibodies (IL-1 alpha, 0.01 microg/ml; IL-1 beta, 0.1 microg/ml) had no effect on strain-induced morphological changes such as elongation and alignment. We conclude that mechanical strain induces IL-1 mRNA expression in keratinocytes. The role of IL-1 in mediating strain-induced changes in keratinocyte biology remains to be determined but appears to be independent of morphological changes.
Takei
T
T
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Kito
H
H
Du
W
W
Mills
I
I
Sumpio
B E
BE
D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D048429:Cell Size / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D015603:Keratinocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D013314:Stress, Mechanical
D000906:Antibodies; D006131:Growth Inhibitors; D007375:Interleukin-1