STIM/Orai-mediated calcium entry elicits spontaneous TSLP overproduction in epidermal cells of atopic dermatitis mice-Reference-Cited by-同舟云学术

STIM/Orai-mediated calcium entry elicits spontaneous TSLP overproduction in epidermal cells of atopic dermatitis mice

Published:2023-06-11 Issue: Volume: Page:174-185
ISSN:2768-6655
Container-title:Exploration of Immunology
language:en
Short-container-title:Explor Immunol

Author:

Fujii Masanori¹^ORCID,Kobayashi Shuhei¹,Ueda Ayane¹,Sakagami Misaki¹,Matsui Rieko¹,Yamada Yumeka¹,Nabe Takeshi²^ORCID,Ohya Susumu³^ORCID

Affiliation:

1. Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan

2. Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan; Laboratory of Immunopharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan

3. Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan; Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan

Abstract

Aim: Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease. Thymic stromal lymphopoietin (TSLP) is highly expressed in the epidermis of patients with AD and induces T helper 2 (Th2) immune responses and itching. Although the mechanism underlying the stimulus-induced TSLP production in normal keratinocytes has been intensively studied, whether the production capability of TSLP is naturally enhanced in epidermal cells in AD conditions remains unclear. Previous studies demonstrated that a deficiency of polyunsaturated fatty acid (PUFA) causes AD-like pruritic skin inflammation in special diet-fed hairless mice. The aim of the study was to examine the TSLP production capability of epidermal cells isolated from diet-induced AD mouse model and its mechanism. Methods: Epidermal cells were isolated from normal and AD mice and incubated under unstimulated culture conditions to assess spontaneous TSLP production. Messenger ribonucleic acid (mRNA) and protein levels of TSLP were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: TSLP level was markedly increased in the skin of AD mice. When epidermal cells were isolated from AD mice and cultured without stimulation, Tslp gene expression was upregulated, and a large amount of TSLP protein was extracellularly released. Such TSLP overproduction was not observed in the epidermal cells of normal mice. TSLP overproduction in AD epidermal cells was almost completely inhibited by extracellular calcium chelation, interference with plasma membrane interaction of stromal interaction molecule 1 (STIM1), blockade of the calcium release-activated calcium (CRAC) channels Orai1 and Orai2, or treatment with a PUFA γ-linolenic acid (GLA). Conclusions: Epidermal cells isolated from AD mice can spontaneously produce TSLP through STIM/Orai-mediated calcium entry, and GLA may negatively regulate this TSLP production.

Publisher

Open Exploration Publishing

Reference48 articles.

1. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396:345–60. Erratum in: Lancet. 2020;396:758.

2. Nakahara T, Kido-Nakahara M, Tsuji G, Furue M. Basics and recent advances in the pathophysiology of atopic dermatitis. J Dermatol. 2021;48:130–9.

3. Fujii M. Current understanding of pathophysiological mechanisms of atopic dermatitis: interactions among skin barrier dysfunction, immune abnormalities and pruritus. Biol Pharm Bull. 2020;43:12–9.

4. Dubin C, Del Duca E, Guttman-Yassky E. The IL-4, IL-13 and IL-31 pathways in atopic dermatitis. Expert Rev Clin Immunol. 2021;17:835–52.

5. Nakajima S, Tie D, Nomura T, Kabashima K. Novel pathogenesis of atopic dermatitis from the view of cytokines in mice and humans. Cytokine. 2021;148:155664.