BACKGROUND: The skin cholinergic signalling system is modulated in atopic dermatitis (AD). OBJECTIVES: To investigate of the role of nicotinic acetylcholine receptors (nAChRs) in the pathogenesis of AD. METHODS: We investigated the expression and localization of nAChR alpha subunits in AD by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry of biopsies from lesional and nonlesional areas of AD skin and of skin biopsies from healthy control persons. RESULTS: Our data demonstrate the presence of mRNA and protein of the nAChR alpha subunits 3, 5, 7, 9 and 10 in keratinocytes and mast cells in healthy and AD skin. Expression of the alpha subunits 3, 7, 9 and 10 was generally reduced in the skin of patients with AD whereas mast cells in AD but not in healthy skin showed alpha3 and alpha5 subunit immunoreactivity. Differences in the subunit mRNA levels between lesional and nonlesional skin were obtained for the alpha subunits 3, 9 and 10 with higher levels of alpha3 but lower levels of alpha10 subunit mRNA in lesional areas. No differences in the expression of the alpha subunits was found between the groups of extrinsic, intrinsic or mixed AD types, between genders and between smokers and nonsmokers. CONCLUSIONS: This supports the idea that the cholinergic system is dysregulated independently from inflammation in AD and that inflammation further modulates individual nAChR subunits.
BACKGROUND: The skin cholinergic signalling system is modulated in atopic dermatitis (AD). OBJECTIVES: To investigate of the role of nicotinic acetylcholine receptors (nAChRs) in the pathogenesis of AD. METHODS: We investigated the expression and localization of nAChR alpha subunits in AD by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry of biopsies from lesional and nonlesional areas of AD skin and of skin biopsies from healthy control persons. RESULTS: Our data demonstrate the presence of mRNA and protein of the nAChR alpha subunits 3, 5, 7, 9 and 10 in keratinocytes and mast cells in healthy and AD skin. Expression of the alpha subunits 3, 7, 9 and 10 was generally reduced in the skin of patients with AD whereas mast cells in AD but not in healthy skin showed alpha3 and alpha5 subunit immunoreactivity. Differences in the subunit mRNA levels between lesional and nonlesional skin were obtained for the alpha subunits 3, 9 and 10 with higher levels of alpha3 but lower levels of alpha10 subunit mRNA in lesional areas. No differences in the expression of the alpha subunits was found between the groups of extrinsic, intrinsic or mixed AD types, between genders and between smokers and nonsmokers. CONCLUSIONS: This supports the idea that the cholinergic system is dysregulated independently from inflammation in AD and that inflammation further modulates individual nAChR subunits.
Authors: Neerad C Mishra; Jules Rir-sima-ah; R Thomas Boyd; Shashi P Singh; Sravanthi Gundavarapu; Raymond J Langley; Seddigheh Razani-Boroujerdi; Mohan L Sopori Journal: J Immunol Date: 2010-05-26 Impact factor: 5.422