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Down-regulation of protein kinase C isoforms in irritant contact dermatitis
1Department of Dermatology, University of Illinois at Chicago, 60612, USA.
Abstract:
Protein kinase C (PKC) isoforms are important in cell signal transduction associated with regulation of cell proliferation and differentiation. In this study, alterations of PKC isoform levels in irritant patch test reactions were detected by Western immunoblots. 4 chemically and structurally different irritants, 4% and 8% hydrochloric acid (HCl); 1% and 2% sodium hydroxide (NaOH); 20% and 40% nonanoic acid (NON) in 1-propanol; and 5% and 10% sodium dodecyl sulfate (SDS) were applied on the backs of mice in Finn Chambers and fixed with surgical dressings. The patches were kept on the skin for 24 h and removed. 24 h after removal, mild erythema with thickening of skin without vesicles was observed in all irritated skin, except that 4% HCl and 1% NaOH treated skin showed unremarkable skin reaction. No visible skin reaction was detected in vehicle-treated skin. PKC isoform alpha, beta, gamma, and delta levels in irritated skin revealed a 10% to 65% decrease compared to vehicle treated skin. These results indicate that in HCl, NaOH, NON and SDS-induced irritation, activation of the PKC related cell signal transduction cascade may be involved, and that PKC mediated events may be a common phenomenon in irritant contact dermatitis.
Insights
Protein kinase C (PKC) levels decrease in skin irritation caused by common chemicals. This suggests PKC signaling pathways are involved in irritant contact dermatitis, impacting cell proliferation and differentiation.
Area of Science:
- Dermatology
- Cell Biology
- Biochemistry
Background:
- Protein kinase C (PKC) isoforms regulate crucial cellular processes like proliferation and differentiation.
- PKC signaling is implicated in various skin conditions, but its role in irritant contact dermatitis is not fully understood.
Purpose of the Study:
- To investigate alterations in PKC isoform levels during irritant patch test reactions.
- To determine the involvement of PKC signaling in chemically induced skin irritation.
Main Methods:
- Mice were subjected to patch tests using hydrochloric acid (HCl), sodium hydroxide (NaOH), nonanoic acid (NON), and sodium dodecyl sulfate (SDS).
- Skin reactions were assessed 24 hours post-application.
- PKC isoform levels (alpha, beta, gamma, delta) in irritated skin were quantified using Western immunoblots.
Main Results:
- Irritant exposure, except for mild HCl and NaOH concentrations, induced erythema and skin thickening.
- PKC isoform levels significantly decreased (10%–65%) in irritated skin compared to controls.
- No visible skin reactions were observed in vehicle-treated skin.
Conclusions:
- Chemically induced skin irritation involves alterations in PKC isoform expression.
- PKC signaling pathways are likely activated during irritant contact dermatitis.
- PKC-mediated events may represent a common mechanism in the pathogenesis of irritant contact dermatitis.