☆ 4.6 Article

RIPK1 downregulation in keratinocyte enhances TRAIL signaling in psoriasis

JOURNAL OF DERMATOLOGICAL SCIENCE (2018)

Journal

JOURNAL OF DERMATOLOGICAL SCIENCE

Volume 91, Issue 1, Pages 79-86

Publisher

ELSEVIER IRELAND LTD

DOI: 10.1016/j.jdermsci.2018.04.007

Keywords

RIPK1; TRAIL; Psoriasis vulgaris; IMQ-model mice

Funding

JSPS KAKENHI [15K19669, 24591620]
Lydia O'leary Memorial Pias Dermatological Foundation
Grants-in-Aid for Scientific Research [15K19669, 15K08582, 24591620] Funding Source: KAKEN

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

Abstract

Background: Psoriasis, a common inflammatory skin disorder characterized by scaly erythema and plaques, is induced by dysregulation of dendritic cell- and T cell-mediated immune reaction. Receptor interacting protein kinase 1 (RIPK1) regulates inflammatory signaling in response to stimuli such as TNF-alpha, TRAIL, and TLRs, resulting in apoptosis, necroptosis and NF-kappa B activation. However, the physiological relevance in human epidermis remains elusive. Objective: In this study, we examined whether RIPK1 is involved in the pathogenesis of psoriasis vulgaris. Methods: Skin samples of eight patients with psoriasis vulgaris were investigated by western blotting and immunohistochemistry. The functions of RIPK1 in keratinocytes were examined by RT-PCR and ELISA in vitro. TRAIL-neutralization-experiment was employed in an imiquimod-induced murine psoriasis model. Results: In lesional psoriatic epidermis, RIPK1-expression was decreased compared with that in normal epidermis. Cytokines involved in the pathomechanism of psoriasis, such as IL-1 beta, IL-17A, IL-22 and TRAIL, reduced RIPK1-expression in normal human epidermal keratinocytes (HEK) in vitro. In addition, RIPK1-knockdown enhanced TRAIL-mediated expression of psoriasis-relating cytokines, such as IL-1 beta, IL-6, IL-8, TNF-alpha, in HEK. Numerous TRAIL-positive cells were detected in the dermis of lesional psoriatic skin, and TRAIL receptors were expressed in psoriatic epidermis and HEK in conventional cultures. Moreover, TRAIL-neutralization in an imiquimod-induced murine psoriasis model remarkably improved skin phenotypes, such as ear thickness, and TNF-alpha expression in lesional skin. Conclusions: These results lead us to conclude that RIPK1-downregulation in keratinocytes increases their susceptibility to TRAIL stimulation, and plays a role in the pathogenesis of psoriasis vulgaris. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Authors

I am an author on this paper

Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6

Not enough ratings

Secondary Ratings

Novelty

Significance

Scientific rigor

Rate this paper

Dose-Response Efficacy and Mechanisms of Orally Administered Bifidobacterium breve CCFM683 on IMQ-Induced Psoriasis in Mice

Xinqi Chen, Yang Chen, Catherine Stanton, Reynolds Paul Ross, Jianxin Zhao, Wei Chen, Bo Yang

Summary: This study aimed to investigate the dose-response effect of Bifidobacterium breve CCFM683 on relieving psoriasis and its underlying patterns. Specifically, the expression of keratin 16, keratin 17, and involucrin were substantially decreased by specific doses of the probiotic. Moreover, the gut microbiota in mice treated with the probiotic was rebalanced and the concentrations of colonic bile acids were positively correlated with the effectiveness of the strain in relieving psoriasis.

NUTRIENTS (2023)