Parasympathetic modulation of amylase secretion by IFNγ in murine submandibular glands

Abstract

IFNγ is a pleiotropic cytokine that exerts immunologic and non-immunologic functions. We show here that at low doses (10 U/ml), it stimulates amylase secretion in murine submandibular glands (SMG) “via” muscarinic receptor activation, comparable to that produced by the muscarinic agonist carbachol. Both effects are blocked by atropine. N G-monomethyl- l-arginine ( l-NMMA) and EGTA inhibited the cytokine effect on amylase secretion, involving the participation of a calcium-dependent isoform of nitric oxide synthase (NOS). We confirm NOS activation because IFNγ stimulates nitrite production and enzyme activity in SMG. Carbachol (10 −7 M) did not modify basal nitric oxide production. In addition, both IFNγ and carbachol increase prostaglandin E 2 production in SMG, but while indomethacin potentiates IFNγ effect on amylase secretion, it blunted amylase secretion exerted by carbachol. Thus, IFNγ and carbachol stimulate IFNγ secretion on SMG in a dose-dependent manner. Our results are pointing to neuroregulatory functions of IFNγ in murine SMG, because it regulates its own levels in oral cavity, perhaps to exert a local immuno-surveillance.