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

Abstract

BackgroundAtopic 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.ObjectiveHere, we evaluate the possibility to manipulate the immune activation of AD keratinocytes and their response to the electromagnetic field, which was not tested before.MethodsKeratinocytes 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.ResultsThis 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.ConclusionApoptotic 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.

Use of Physcion to Improve Atopic Dermatitis-Like Skin Lesions through Blocking of Thymic Stromal Lymphopoietin

“…Thus, we presume that physcion may be beneficial to prevent and/or treat atopic diseases. Patients with AD possess higher levels of proinflammatory cytokines such as IL-6, TNF-α, IL-1β, IL-4, and IFN-γ [33,34,35]. Our results showed that physcion suppresses the levels of IL-6, TNF-α, IL-1β, IL-4, and IFN-γ, suggesting the potential of physcion in the treatment of AD.…”

Experimental atopic dermatitis is dependent on the TWEAK/Fn14 signaling pathway

“…Moreover, TWEAK and TNF‐α co‐operate in the induction of keratinocyte apoptosis . Considering that TNF‐α is abundant in skin tissue of atopic dermatitis , our results explained the reduction of keratinocyte apoptosis in Fn14‐deficient skin of an atopic dermatitis model. We further elucidated that, as well as the anti‐inflammatory role, the inhibition of TWEAK/Fn14 interaction exerts its therapeutic effects by altering the TNFR1/TNFR2 expression profile, which may generate cell‐fate diversity of keratinocytes under different inflammatory contexts.…”

“…As well as these proinflammatory effects, extensive apoptosis of keratinocytes is one of the histological features in atopic dermatitis . We found that apoptotic cells decrease in skin lesions of Fn14‐deficient mice.…”

Effects of Acute and Chronic Exposure to 900 Mhz Electromagnetic Field on the Rat Liver Microarchitecture

“…The interaction of the living organisms and EMF can occur via changes the activation of the channel and pumps in the cell membrane, so the cell ionic balance is rearranged [6]. EMF changes cell function via mainly oxidative stress biochemical cascades, intense apoptosis and other vital properties [7,8]. Reactive oxygen species (ROS) occurs in oxidative reactions to produce energy in metabolic and physiological processes in the organism.…”