Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium

Abstract

The human calcium-binding protein (hS100A15) was first identified in inflamed hyperplastic psoriatic skin, where the S100A15 gene is transcribed into two mRNA splice variants, hS100A15-S and hS100A15-L. To compare the contribution of the human S100A15 (hS100A15) isoforms in skin inflammation and differentiation, we determined the expression, distribution and regulation of hS100A15-S and hS100A15-L in psoriasis and chronic atopic eczema compared with normal skin. We found that both hS100A15 transcripts were mainly distributed in the epidermis of normal and inflamed skin with hS100A15-L being the predominantly expressed mRNA isoform in both psoriasis and atopic eczema. In cultured keratinocytes, IL-1beta and Th1 cytokines significantly induced hS100A15-L compared with hS100A15-S. In contrast, Th2-derived cytokines had no influence on the expression of either hS100A15 splice variant. Differentiation of human keratinocytes induced by 1.2 mm calcium resulted in the upregulation of both hS100A15 mRNA isoforms. Our data show that both hS100A15 splice variants are differentially regulated and expressed with epidermal differentiation and skin inflammation. Overexpression of hS100A15 in chronic inflammatory skin diseases and regulation by inflammatory cytokines and calcium suggest that hS100A15 is involved in Th1-associated epithelial responses and epidermal maturation in normal and diseased human skin.

Leukocyte-derived koebnerisin (S100A15) and psoriasin (S100A7) are systemic mediators of inflammation in psoriasis

“…They act as proinflammatory danger molecules 'alarmins' on keratinocytes and as chemoattractants for leukocytes to potentiate inflammation in the skin. Overexpressed in psoriatic lesions, they synergize through their distinct expression and functional mechanisms and contribute to the development of skin lesions [10][11][12][13][14][15]. In the present study we investigated the expression of koebnerisin and psoriasin in human Here, we demonstrated for the first time that koebnerisin and psoriasin were expressed by human leukocytes from peripheral blood showing cell type-specific expression patterns.…”

“…3E-G). Data suggest that circulating, migratory leukocytes may contribute to the increased levels of koebnerisin and psoriasin observed in both skin lesions and in serum of patients with psoriasis [14,15,23].…”

“…Both S100A proteins are overexpressed in the epidermal suprabasal compartment of psoriatic lesions, whereas koebnerisin is additionally expressed by basal keratinocytes as well as by other cell types in the dermis. The epidermal expression of both proteins is differently induced by Th1-, Th17-and Th22-derived cytokines that create a characteristic psoriatic micro-milieu [10,[13][14][15]. Overexpressed in psoriatic skin lesions, koebnerisin and psoriasin promote inflammatory processes in the skin.…”

“…The koebnerisin gene reveals a unique genomic organization and is transcribed into two alternate splice variants, S100A15-S (short) and S100A15-L (long), which share the same coding region. Both S100A15 transcripts are differentially expressed in the psoriatic skin suggesting regulation through alternate promoters with a predominant expression of S100A15-L variant in the skin [14].…”

Dermal dendritic cells in psoriasis, nummular dermatitis, and normal-appearing skin

“…We chose to analyze the S100 A6 and A4 subtypes in this study because we had observed variability in their expression in dendritic-appearing dermal cells incidentally during the course of an unrelated study, and some evidence suggests S100 proteins are involved in PSO [29][30][31] and that their expression may differ among PSO, normalappearing skin, and other inflammatory conditions including contact dermatitis. 32,33 Although the values approached significance, S100A6 1 cells were not significantly different between PSO and normalappearing skin or between ND and normalappearing skin.…”