Participation of Protein Nitration in Keratotic Plug Formation

Abstract

A keratotic plug (KP) is a solid mass primarily composed of protein that forms in pores, and preventing their formation has been challenging. The presence of keratin 17 (K17), a characteristic of KPs, implies the involvement of interferon-gamma (IFN-γ), which contributes to K17 formation, in KP formation. IFN-γ is also involved in the production of nitric oxide (NO), and NO-mediated nitration of tyrosine is known to induce protein aggregation, which is one of the possible mechanisms by which proteins become solids. In this study, to clarify the involvement of IFN-γ and protein nitration in KPs, we investigated the relationship between the amount of IFN-γ collected from the skin around nasal alae and the number of KPs, protein components of KPs, and the effect of nitration on molecular sizes of proteins in vitro. As a result, more KPs were detected in individuals with high IFN-γ levels, and nitrotyrosine was present within the KPs. Protein nitration increased the molecular size of proteins, and IFN-γ increased nitrotyrosine production in keratinocytes in the same manner as in NO donors. Collectively, these findings indicate that IFN-γ-mediated protein nitration via NO generation causes solid mass formation in the pores. Inhibition of protein nitration followed by protein aggregation could be effective in preventing KP formation.