Neuronal nitric oxide synthase mediates the effect of ethanol on IgA.
OBJECTIVE
We showed previously that the acute effect of ethanol on intestinal immunoglobulin A (IgA) expression might be mediated by endogenous nitric oxide (NO). To extend these findings, this study was designed to investigate a possible role of neuronal NO synthase (nNOS) in the observed phenomenon, using 7-nitroindazole (7-NI), a selective inhibitor of its activity.


METHODS
Adult male Wistar rats were treated with: (a) ethanol (4 g/kg, intraperitoneally, i.p.), (b) 7-NI (25 mg/kg, i.p.) followed by ethanol (4 g/kg, i.p.) 30 min later and (c) 7-NI (25 mg/kg, i.p.) followed by saline 30 min later. Untreated rats were used as controls. The concentrations of serum and intestinal IgA were measured by enzyme-linked immunosorbent assay, while the expression of nNOS was determined using western blot and immunohistochemistry.


RESULTS
Acute ethanol treatment significantly increased the concentration of IgA in the ileal extracts, whereas it decreased its serum level. Inhibition of nNOS activity by 7-NI abolished this action of alcohol on IgA. Additionally, western blot analysis revealed that the acute alcohol administration induced an increase in the expression of intestinal nNOS. Furthermore, nNOS-immunoreactive cells, observed within the lamina propria of small intestine, were numerous in ethanol-treated rats.


CONCLUSIONS
Taken together, these results extended our previous findings suggesting that nNOS mediates the acute effect of ethanol on IgA and supported an immunomodulatory role of this enzyme isoform.
University of Belgrade, Institute for Medical Research, Dr Subotića 4, Belgrade 102, Serbia. mirelab@imi.bg.ac.rs
Mirela
M
Budec
Dragana
D
Markovic
Sanja
S
Vignjevic
Olivera
O
Mitrovic
Dragoslava
D
Dikic
Vesna
V
Koko
Vladan P
VP
Cokic
D000818:Animals; D015415:Biomarkers / Q000097:blood; D000431:Ethanol / Q000633:toxicity*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007070:Immunoglobulin A / Q000378:metabolism*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D007070:Immunoglobulin A; D000431:Ethanol; D052248:Nitric Oxide Synthase Type I