The antimicrobial protein S100A7/psoriasin enhances the expression of keratinocyte differentiation markers and strengthens the skin's tight junction barrier

Hattori, Fumihiro; Kiatsurayanon, Chanisa; Okumura, Ko; Ogawa, Hideoki; Ikeda, Shigaku; Okamoto, Kikuhiko; Niyonsaba, François

doi:10.1111/bjd.13125

Cited by 57 publications

(62 citation statements)

References 59 publications

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“…[42, 43] In human cultured keratinocytes, hS100A7 also induce the expression of several differentiation markers, which are overexpressed in psoriatic skin. [44, 45] In our study, we confirmed that mS100a7a15 was overexpressed in psoriasis model skin. Mature IL-1α, not IL-1β, is induced by hS100A7 stimulation in keratinocytes, and mature IL-1α is also detected in in vivo .…”

Section: Discussionsupporting

confidence: 81%

Human S100A7 Induces Mature Interleukin1α Expression by RAGE-p38 MAPK-Calpain1 Pathway in Psoriasis

Jing

et al. 2017

PLoS ONE

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Psoriatic keratinocytes express exaggerated levels of inflammatory cytokines, and show aberrant hyperproliferation and terminal differentiation in the pathogenesis of psoriasis. The antimicrobial protein hS100A7 (psoriasin) has been found highly expressed in psoriatic skin, but the mechanism and physiological function remain largely unknown. We observed that hS100A7 induces mature interleukin 1α (17kDa) expression in normal human epidermal keratinocytes, which is dependent on RAGE-p38 MAPK and calpain-1 as the inhibitors or knockdown of them completely decreased the expression of mature interleukin1α. Then, we proved mS100a7a15, mature IL-1α and calpain-1 were highly expressed in imquimod-induced psoriasis model and mouse IL-17a-neutralizing antibody treatment attenuated mS100a7a15 expression. At last, PD 151746 (calpain-1 inhibitor) treatment decreased epidermal thickness in imquimod-induced psoriasis model. Taken together, our results suggest that mature IL-1α induced by hS100A7 is via RAGE-p38 MAPK and calpain-1 pathway in keratinocyte and this mechanism may play an important role during psoriasis.

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Section: Discussionsupporting

confidence: 81%

Human S100A7 Induces Mature Interleukin1α Expression by RAGE-p38 MAPK-Calpain1 Pathway in Psoriasis

Jing

et al. 2017

PLoS ONE

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“…In addition, while Hattori et al . employed a high calcium concentration (1.25 m m ) to induce differentiation, we used a low calcium concentration (0.1 mM CaCl 2 ) and induced density‐dependent differentiation of keratinocytes in which epidermal differentiation markers such as KRT1 and KRT10 were increased (Fig. S2a).…”

Section: Discussionmentioning

confidence: 99%

S100A7 (psoriasin) inhibits human epidermal differentiation by enhanced IL‐6 secretion through IκB/NF‐κB signalling

Son

Kim

et al. 2016

Experimental Dermatology

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Psoriasin (S100A7), a member of the S100 protein family, is a well-known antimicrobial peptide and a signalling molecule which regulates cellular function and is highly expressed in hyperproliferative skin conditions such as atopic dermatitis (AD) and psoriasis with disrupted skin barrier function. However, its role in epidermal differentiation remains unknown. We examined the effect of S100A7 on epidermal differentiation in normal human keratinocytes (NHKs) and on a reconstituted human epidermis model. When NHKs were exposed to disruptive stimuli such as Staphylococcus aureus, ultraviolet irradiation and retinoic acid, the secretion of S100A7 into the culture medium increased and the expression of epidermal differentiation markers decreased. Treatment of NHKs with S100A7 significantly inhibited epidermal differentiation by reducing the expression of keratin 1, keratin 10, involucrin and loricrin and by increasing the expression of abnormal differentiation markers (keratin 6 and keratin 16). We verified that the MyD88-IκB/NF-κB signal cascade was activated via RAGE after S100A7 treatment, resulting in the upregulation of interleukin-6. Finally, we confirmed that S100A7 is a negative regulator of epidermal differentiation using a reconstituted human epidermis model. This study suggests that S100A7-related signalling molecules could be potent targets for recovering skin barrier function in AD and psoriasis where S100A7 is accumulated excessively.

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“…55 Recent studies in cultured keratinocytes have also shown that other innate mediators, such as antimicrobial peptides (AMPs) including S100A7, LL-37 and HBD3 enhance TJ protein expression and TJ function (TER and macromolecule tracer permeability) thus contributing to repair and possibly even maintain homeostatic barrier function. [56][57][58] It is important to note that the aforementioned studies utilized bacterial-derived peptidoglycan or synthetic TLR2-ligands, in an otherwise "sterile" environment and these stimulations were done during TJ assembly (e.g., wound repair model or differentiation of keratinocytes). The situation can be quite different and more complex when using whole bacteria or when evaluating the effect in full thickness epithelium with fully mature TJs.…”

Section: Tj and Innate Immune Barriermentioning

confidence: 99%

Epidermal tight junctions in health and disease

et al. 2014

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The antimicrobial protein S100A7/psoriasin enhances the expression of keratinocyte differentiation markers and strengthens the skin's tight junction barrier

Abstract: Our finding that S100A7/psoriasin regulates differentiation and strengthens TJ barrier function provides novel evidence that, in addition to antimicrobial and immunoregulatory activities, S100A7/psoriasin is involved in skin innate immunity.

Cited by 57 publications

References 59 publications

Human S100A7 Induces Mature Interleukin1α Expression by RAGE-p38 MAPK-Calpain1 Pathway in Psoriasis

Human S100A7 Induces Mature Interleukin1α Expression by RAGE-p38 MAPK-Calpain1 Pathway in Psoriasis

S100A7 (psoriasin) inhibits human epidermal differentiation by enhanced IL‐6 secretion through IκB/NF‐κB signalling

Epidermal tight junctions in health and disease

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