Down‐regulation of protein kinase C isoforms in irritant contact dermatitis

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.

Metallothionein I and II gene knock-out mice exhibit reduced tolerance to 24-h sodium lauryl sulphate patch testing

“…Test concentrations were chosen according to the published literature to obtain mild to severe skin-irritant reactions. 10 Closed patch test and harvesting of skin samples…”

Nociceptive-induced myocardial remote conditioning is mediated by neuronal gamma protein kinase C

“…How γPKC mediates the signal caused by the abdominal intervention to the heart is likely through the highly innervated abdominal skin, since γPKC was present in homogenized mouse skin transmitting a signal to the spinal cord [27]. This is supported by findings that a neuronal specific fluorescent dye, dil, locally injected to the abdominal skin at the same site of our abdominal incision travels from the abdominal neurons, to the spinal cord, and up to nerve endings innervating the heart at T1-T4 [25].…”

Experimental Validation of a Structure–Activity Relationship Model of Skin Irritation by Esters

“…Skin irritation may be caused by chemicals with vastly different structures and physicochemical properties, including detergents, solvents, organic and inorganic acids and bases, alcohols, and esters. The mechanisms responsible for generating the in¯ammatory skin response also involve a number of factors, including production and release of cytokines [7±9] and eicosanoids [10,11] as well as activation of protein kinase C [12]. The speci®c mechanistic pathway likely varies with chemical type.…”