Fas/FasL pathway and cytokines in keratinocytes in atopic dermatitis - Manipulation by the electromagnetic field.
← Research streamKeratinocytes from atopic dermatitis (AD) patients showed higher Fas/FasL and MAPK pathway phosphorylation markers (p-ERK, p-p38, p-JNK) and increased secretion of multiple cytokines compared with healthy controls. After 900 MHz EMF exposure for 60 minutes, A…
Study snapshot
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.
AI evidence extraction
Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.
Main findings
Keratinocytes from atopic dermatitis (AD) patients showed higher Fas/FasL and MAPK pathway phosphorylation markers (p-ERK, p-p38, p-JNK) and increased secretion of multiple cytokines compared with healthy controls. After 900 MHz EMF exposure for 60 minutes, AD-derived keratinocyte cultures showed decreased levels of several cytokines (IL-1β, IL-4, IL-10, IL-12, IL-13, IL-17, IL-31, TNFα).
Outcomes measured
- Keratinocyte viability
- Fas (CD95) expression
- FasL (CD178) expression
- p-ERK expression
- p-p38 expression
- p-JNK expression
- Cytokine concentrations (IL-1β, IL-4, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-31, TNFα) at 4 and 24 hours post-exposure
Limitations
- In vitro study; findings may not translate to clinical outcomes in humans
- Exposure metric details (e.g., SAR, field strength) not reported in the abstract
- Direction of EMF effects on some measured endpoints (e.g., Fas/FasL, MAPK markers, IL-8) after exposure not clearly stated in the abstract
- Only two post-exposure time points (4 and 24 hours) reported
View raw extracted JSON
{
"study_type": "in_vitro",
"exposure": {
"band": "RF",
"source": null,
"frequency_mhz": 900,
"sar_wkg": null,
"duration": "60 minutes"
},
"population": "Primary human keratinocytes isolated from healthy subjects (n=20) and patients with atopic dermatitis (n=20); also HaCaT and PCS-200-010 cell lines",
"sample_size": 40,
"outcomes": [
"Keratinocyte viability",
"Fas (CD95) expression",
"FasL (CD178) expression",
"p-ERK expression",
"p-p38 expression",
"p-JNK expression",
"Cytokine concentrations (IL-1β, IL-4, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-31, TNFα) at 4 and 24 hours post-exposure"
],
"main_findings": "Keratinocytes from atopic dermatitis (AD) patients showed higher Fas/FasL and MAPK pathway phosphorylation markers (p-ERK, p-p38, p-JNK) and increased secretion of multiple cytokines compared with healthy controls. After 900 MHz EMF exposure for 60 minutes, AD-derived keratinocyte cultures showed decreased levels of several cytokines (IL-1β, IL-4, IL-10, IL-12, IL-13, IL-17, IL-31, TNFα).",
"effect_direction": "mixed",
"limitations": [
"In vitro study; findings may not translate to clinical outcomes in humans",
"Exposure metric details (e.g., SAR, field strength) not reported in the abstract",
"Direction of EMF effects on some measured endpoints (e.g., Fas/FasL, MAPK markers, IL-8) after exposure not clearly stated in the abstract",
"Only two post-exposure time points (4 and 24 hours) reported"
],
"evidence_strength": "low",
"confidence": 0.78,
"peer_reviewed_likely": "yes",
"keywords": [
"atopic dermatitis",
"keratinocytes",
"Fas",
"FasL",
"cytokines",
"immunomodulation",
"MAPK",
"p-ERK",
"p-p38",
"p-JNK",
"900 MHz",
"radiofrequency",
"electromagnetic field"
],
"suggested_hubs": []
}AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.
Identifiers and source
DOI: 10.1371/journal.pone.0205103
PubMed: 30286163
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