Nicotine affects tight junction barriers via alpha7 nicotine-like acetylcholine receptor in keratinocytes

Smoking negatively affects the skin, causing wrinkles, dryness, blemishes with delayed wound healing, and decreased barrier function [ Sorensen L.T. Zillmer R. Agren M. Ladelund S. Karlsmark T. Gottrup F. Effect of smoking, abstention, and nicotine patch on epidermal healing and collagenase in skin transudate.

Wound Repair Regen. 2009; 17: 347-353

]. In psoriasis, an immunologically-initiated inflammatory disease, it has been reported that severity is positively correlated with smoking amount and duration [ Lee E.J. Han K.D. Han J.H. Lee J.H. Smoking and risk of psoriasis: A nationwide cohort study, J. Am.

Acad. Dermatol. 2017; 77: 573-575

]. Active and passive exposure to nicotine smoke has also been associated with the prevalence of atopic dermatitis (AD) [ Kantor R. Kim A. Thyssen J.P. Silverberg J.I. Association of atopic dermatitis with smoking: A systematic review and meta-analysis.

J. Am. Acad. Dermatol. 2016; 75: 1119-1125

]. We previously reported that type B ultraviolet, as an extracorporeal stimulus, is involved in the destruction of tight junctions (TJs), which protect the skin barrier from external stimuli [ Yuki T. Hachiya A. Kusaka A. Sriwiriyanont P. Visscher M.O. Morita K. Muto M. Miyachi Y. Sugiyama Y. Inoue S. Characterization of tight junctions and their disruption by UVB in human epidermis and cultured keratinocytes, J. Invest.

Dermatol. 2011; 131: 744-752

]. Here, we focused on the toxic substance nicotine as an internal stimulus that might also affect TJs using an in vitro skin model. Nicotine stimulates nicotine-like acetylcholine receptors (nAChR) in keratinocytes, affecting skin barrier formation; this serves as an indicator of differentiation to the stratum corneum [ Arredondo J. Nguyen V.T. Chernyavsky A.I. Bercovich D. Orr-Urtreger A. Kummer W. Lips K. Vetter D.E. Grando S.A. Central role of alpha7 nicotinic receptor in differentiation of the stratified squamous epithelium.

J. Cell Biol. 2002; 159: 325-336

]. However, no studies have focused on the effects of nAChR on skin TJ function.

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