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Role of SNAREs in Atopic Dermatitis-Related Cytokine Secretion and Skin-Nerve Communication.

Abstract

The role of soluble N-ethylmaleimide-sensitive factor attachment protein receptors in atopic dermatitis (AD) is unknown. This study identifies the function of soluble N-ethylmaleimide sensitive factor attachment protein receptor in AD-related cytokine secretion and epidermis-nerve communication. Herein, we report that various cytokines were simultaneously upregulated and coreleased in innate immunity-activated primary human keratinocytes. AD-related cytokines thymic stromal lymphopoietin, endothelin-1, and inflammatory tumor necrosis factor-α activated distinct but overlapping sensory neurons. Tumor necrosis factor-α potentiated thymic stromal lymphopoietin-induced Ca2+-influx, whereas endothelin-1 caused itch-selective B-type natriuretic peptide release. In primary human keratinocytes, B-type natriuretic peptide upregulated genes promoting dermatological and neuroinflammatory diseases and conditions. VAMP3, SNAP-29, and syntaxin 4 proved important in driving cytokine release from primary human keratinocytes. Depletion of VAMP3 inhibited nearly all the cytokine release including thymic stromal lymphopoietin and endothelin-1. Accordingly, VAMP3 co-occurred with endothelin-1 in the skins of patients with AD. Our study pinpoints the pivotal role of soluble N-ethylmaleimide sensitive factor attachment protein receptors in mediating cytokine secretion related to AD. VAMP3 is identified as a suitable target for developing broad-spectrum anticytokine therapeutics for controlling itch and atopic skin inflammation.

Authors+Show Affiliations

School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland; Department of Dermatology and UCD Charles Institute for Translational Dermatology, Dublin, Ireland. Electronic address: Jianghui.meng@dcu.ie.School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland.Department of Dermatology and Venereology, and Translational Research Institute, Hamad Medical Corporation, Doha, Qatar; Medical School, Qatar University, Doha, Qatar.Department of Dermatology, University Medical Center Göttingen, Göttingen, Germany.Department of Dermatology and UCD Charles Institute for Translational Dermatology, Dublin, Ireland; Department of Dermatology and Venereology, and Translational Research Institute, Hamad Medical Corporation, Doha, Qatar; Medical School, Qatar University, Doha, Qatar; Weill Cornell Medicine-Qatar, School of Medicine, Qatar University, Doha, Qatar; Department of Dermatology, Weill Cornell University, New York, New York, USA. Electronic address: MSteinhoff@hamad.qa.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31128202

Citation

Meng, Jianghui, et al. "Role of SNAREs in Atopic Dermatitis-Related Cytokine Secretion and Skin-Nerve Communication." The Journal of Investigative Dermatology, 2019.
Meng J, Wang J, Buddenkotte J, et al. Role of SNAREs in Atopic Dermatitis-Related Cytokine Secretion and Skin-Nerve Communication. J Invest Dermatol. 2019.
Meng, J., Wang, J., Buddenkotte, J., Buhl, T., & Steinhoff, M. (2019). Role of SNAREs in Atopic Dermatitis-Related Cytokine Secretion and Skin-Nerve Communication. The Journal of Investigative Dermatology, doi:10.1016/j.jid.2019.04.017.
Meng J, et al. Role of SNAREs in Atopic Dermatitis-Related Cytokine Secretion and Skin-Nerve Communication. J Invest Dermatol. 2019 May 23; PubMed PMID: 31128202.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of SNAREs in Atopic Dermatitis-Related Cytokine Secretion and Skin-Nerve Communication. AU - Meng,Jianghui, AU - Wang,Jiafu, AU - Buddenkotte,Joerg, AU - Buhl,Timo, AU - Steinhoff,Martin, Y1 - 2019/05/23/ PY - 2019/01/08/received PY - 2019/04/08/revised PY - 2019/04/23/accepted PY - 2019/5/28/pubmed PY - 2019/5/28/medline PY - 2019/5/26/entrez JF - The Journal of investigative dermatology JO - J. Invest. Dermatol. N2 - The role of soluble N-ethylmaleimide-sensitive factor attachment protein receptors in atopic dermatitis (AD) is unknown. This study identifies the function of soluble N-ethylmaleimide sensitive factor attachment protein receptor in AD-related cytokine secretion and epidermis-nerve communication. Herein, we report that various cytokines were simultaneously upregulated and coreleased in innate immunity-activated primary human keratinocytes. AD-related cytokines thymic stromal lymphopoietin, endothelin-1, and inflammatory tumor necrosis factor-α activated distinct but overlapping sensory neurons. Tumor necrosis factor-α potentiated thymic stromal lymphopoietin-induced Ca2+-influx, whereas endothelin-1 caused itch-selective B-type natriuretic peptide release. In primary human keratinocytes, B-type natriuretic peptide upregulated genes promoting dermatological and neuroinflammatory diseases and conditions. VAMP3, SNAP-29, and syntaxin 4 proved important in driving cytokine release from primary human keratinocytes. Depletion of VAMP3 inhibited nearly all the cytokine release including thymic stromal lymphopoietin and endothelin-1. Accordingly, VAMP3 co-occurred with endothelin-1 in the skins of patients with AD. Our study pinpoints the pivotal role of soluble N-ethylmaleimide sensitive factor attachment protein receptors in mediating cytokine secretion related to AD. VAMP3 is identified as a suitable target for developing broad-spectrum anticytokine therapeutics for controlling itch and atopic skin inflammation. SN - 1523-1747 UR - https://www.unboundmedicine.com/medline/citation/31128202/Role_of_SNAREs_in_the_Atopic_Dermatitis-related_Cytokine_Secretion_and_Skin-Nerve_Communication L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-202X(19)31559-3 DB - PRIME DP - Unbound Medicine ER -