Karaman-Jurukovska N, Hamzavi IH, Kohli I, Nicholson C, Mohammad T, Nahhas A, Braunberger T, Matsui M, and Mammone T. 633 Comparison of soluble proteins from skin sections of acne and TCA induced postinflammatory hyperpigmentation and erythema. J Invest Dermatol 2022; 142(8):S109.
J Invest Dermatol
Postinflammatory hyperpigmentation (PIH) is an acquired hypermelanosis occurring after cutaneous inflammation or injury that can arise in all skin types, but more frequently affects skin-of-color. The differences in the ethology of PIH and Postinflammatory erythema (PIE) in skin of color were evaluated from soluble protein extracts collected from skin section samples, using Somascan protein kit1.3 k (n=5). The skin samples were collected from selected gluteal TCA-induced lesions and truncal acne pustules, of either PIH or PIE, at day 28 post initial evaluation. Differences between proteins (FDR<0.05) from PIH and PIE were analyzed with STRING version 11.5 and analysis points toward involvement of JAK/STAT signaling pathway and enhanced IL17 signaling in PIH compared to PIE lesions (OSM, CSF3, IL10RA, IL12RB2, IL10RB, IL3, CSF2, IL17D, IL17F, IFNA2, IFNA10, CRLF2, IL5RA, TYK2, IL12RB1, PRLR, GHR). The involvement of JAK/STAT signaling pathway has been described for some chronic cutaneous inflammatory conditions and acne. A higher occurrence of dermal remodeling proteases and inhibitors were found in PIE (MMP1, MMP2, MMP7, TIMP2) indicating a dermal remodeling phase at the time of excision. Concurrently, elevated levels of IL-1β, and TGF-β (critical for triggering and continuing differentiation programs of naïve CD4+ T cells to IL-17 secreting Th17 cells) in PIH samples suggests continuing promotion of macrophage infiltration and sustained inflammation. In addition to MMP13 and MMP16, the protein Keap1 was found to be increased in the PIH samples. Keap1, a repressor of master cellular defense against oxidative and electrophilic stresses, has been reported to be involved in the imbalance of proteolysis that can lead towards premature aging and in a senescent phenotype of endothelial cells. The sustained inflammation with excess of Keap1 protein might contribute to an altered proteostasis and ethology of PIH.