Fas/FasL pathway and cytokines in keratinocytes in atopic dermatitis - Manipulation by the electromagnetic field.

Abstract

BACKGROUND:Atopic dermatitis (AD) is one of the most frequent skin diseases. Changes of the keratinocytes functionality play a major role in the development of AD. For example, activation of the Fas (CD95)/FasL (CD178) pathway in AD does not lead to extensive apoptosis in skin. Binding of the Fas receptor to its protein ligand-FasL, which are present on the (AD)-modified keratinocytes, should result in the sequential induction of cell death, but there is no evidence of extensive apoptosis of these cells. This suggests that non-apoptotic mechanism of Fas/FasL pathway is commonly encountered, although not examined in the case of AD, phenomenon. An electromagnetic field, which was used to influence cultured cells in this study, can modulate proliferation, apoptosis, differentiation, and metabolism in various cells. OBJECTIVE:Here, we evaluate the possibility to manipulate the immune activation of AD keratinocytes and their response to the electromagnetic field, which was not tested before. METHODS:Keratinocytes isolated from the skin of healthy subjects (n = 20) and patients with atopic dermatitis (n = 20) as well as HaCaT and PCS-200-010 cell were exposed to the 900 MHz electromagnetic field for 60 minutes. Cytometric analysis of viability, Fas/FasL, p-ERK, p-p38 and p-JNK expression and Luminex analysis of cytokine concentration were performed in two-time points: 4 and 24 hours after the exposition. RESULTS:This research has shown upregulated Fas, FasL, p-ERK, p-p38, and p-JNK expression along with increased cytokine secretion (IL-1β, IL-4, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-31 and TNFα) by keratinocytes derived from the skin of patients with the AD when compared with healthy control. Exposure of keratinocyte cultures obtained from AD patients to EMF resulted in a decrease of 1β, IL-4, IL-10, IL-12, I L-13, IL-17, IL-31 and TNFα levels. Keratinocytes derived from the skin of AD patients are characterized by elevated Fas and FasL expression when compared to healthy control. CONCLUSION:Apoptotic and nonapoptotic activation of the Fas/FasL-dependent signaling pathway may play a significant role in the pathogenesis of AD, by adjusting the local cytokine and chemokine environment at the site of inflammation. Moreover, the electromagnetic field exhibits strong immunomodulatory effects on AD-modified keratinocytes.