Acute cutaneous barrier disruption of the skin elicits various homeostatic repair responses in the epidermis. Although several candidates for the signaling mechanisms that induce these responses have been reported, e.g. the calcium and ion concentration, peroxisome proliferator-activated receptor-α, and TNF-α signaling mediated by sphingomyelinases, the exact nature of the signals remains undetermined. Therefore, assuming that an important group of serine/threonine-signaling kinases, mitogen-activated protein kinases (MAPKs), such as p44/42 MAPK, p38 MAPK, and SAPK/JNK, might link the barrier disruption to the subsequent homeostatic responses, the activation of three MAPKs in hairless guinea pig or in human skin after barrier disruption was investigated. The epidermal barrier was insulted with tape stripping or organic solvents, and the activation of these MAPKs was examined with immunohistochemistry, Western blotting, and immune complex kinase assay. In the skin of hairless guinea pigs, p44/42 MAPK and p38 MAPK, but not SAPK/JNK, were activated in epidermal keratinocytes immediately after tape stripping, and continued to be activated for at least 180 min. The activation of p44/42 MAPK was well correlated with an increase in transepidermal water loss, which was positively correlated with the number of tape strippings, whereas the covering of the stripped skin with occlusive dressing or with Ca2++K++sucrose solution suppressed its activation. The activation of p44/42 MAPK was also induced by treatment of the skin with organic solvents. In a similar fashion, p44/42 and p38 MAPKs were found to be activated in human skin after tape stripping. These results strongly suggest that the activation of p44/42 and p38 MAPKs links the stimuli of barrier disruption to the subsequent homeostatic responses to repair the barrier defect.
ASJC Scopus subject areas
- Molecular Biology