3-nitrotyrosine and Submandibular-Gland-Diseases

Inducible nitric oxide synthase (iNOS) is a key regulator of the innate immune system. The aim of the current study was to explore whether innate immune-mediated iNOS and reactive nitrogen species acutely perturb acinar cell physiology and calcium homeostasis of exocrine salivary tissues.. Innate immunity in the submandibular gland of C57BL/6 mice was locally activated via intraductal retrograde infusion of polyinosinic:polycytidylic acid (poly (I:C). Expressions of iNOS and the activity of the reactive nitrogen species peroxynitrite, were evaluated by immunohistochemistry. Mice were pre-treated with the selective iNOS inhibitor aminoguanidine in order to substantiate the injurious effect of the nitrosative signal on the key calcium regulator sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2b) and calcium signalling.. Challenging salivary gland innate immunity with poly (I:C) prompted upregulated expression of iNOS and the generation of peroxynitrite. Inhibition of iNOS/peroxynitrite revealed the role played by upregulated nitrosative signalling in: dysregulated expression of SERCA2b, perturbed calcium homeostasis and loss of saliva secretion.. iNOS mediates disruption of exocrine calcium signalling causing secretory dysfunction following activation of innate immunity in a novel salivary gland injury model.

Topics: Acinar Cells; Animals; Calcium; Calcium Signaling; Enzyme Inhibitors; Female; Guanidines; Immunity, Innate; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Nitrosative Stress; Peroxynitrous Acid; Poly I-C; Saliva; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Submandibular Gland; Submandibular Gland Diseases; Tyrosine; Up-Regulation