Induction of interleukin (IL)-1α and β gene expression in human keratinocytes exposed to repetitive strain: Their role in strain-induced keratinocyte proliferation and morphological change

Abstract

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.

Cytokine and chemokine release upon prolonged mechanical loading of the epidermis

“…These results correspond well to studies performed by Lee et al. and Takei et al., which showed that the mechanical straining of keratinocyte monolayers promotes the expression and release of IL‐1 α and IL‐1RA (9,33). An increase in cytokines, such as IL‐1 α and TNF‐ α was also found in studies in which the epidermal tissue was irritated and/or injured by applying various chemicals, UV irradiation or by tape stripping (14,34–39).…”

Induction of p38, tumour necrosis factor-α and RANTES by mechanical stretching of keratinocytes expressing mutant keratin 10R156H

“…25,29 These mechanisms are partially controlled by quick cytokine release to the body fluid from residual cells. [30][31][32][33] Indeed, IL-1 release has already been reported in stretched keratinocytes, 34 supporting our results and validating the keratinocyte mechanosensation in the presented system. Moreover, some cytokines such as IL-1b, IL-6 or TNF-a have already been reported to contribute to the pathogenesis of skin disorders related to mutations in keratin genes, such as epidermolysis bullosa simplex (EBS).…”

Hypotonic stress influence the membrane potential and alter the proliferation of keratinocytes in vitro

“…In addition to growth factors, which are known to mediate the proliferation and differentiation of keratinocytes (35), mechanical stress has also been assumed to cause alterations in their proliferation and was shown to affect cell growth in vitro (5,36). Several signalling pathways were found to be altered by mechanical stimulation including isoform‐specific PKC activation (37) and induction of interleukin‐1 α and β gene expression (38). Recent experiments established a link between hyperosmotic stress and reduced proliferation rate in HaCaT (39) as well as by resveratrol‐induced cell cycle arrest in p53 mutant keratinocytes (40).…”