NOD mice exocrinopathy: towards a neuroimmune link.
Sjogren's syndrome (SS) is a chronic autoimmune disorder of exocrine glands characterized as an autoimmune exocrinopathy and more specifically as an autoimmune epithelitis. An impaired balance of neuroimmune interactions mediated by vasoactive intestinal peptide (VIP) in the target organ at early stages of disease is explored by means of the nonobese diabetic (NOD) mouse model of SS. We have previously described a reduced salivary secretion and signaling upon VIP stimulation. The effect reflected a differential regulation of the neural isoform of nitric oxide synthase by calcium calmodulin kinase II and occurred prior to the appearance of detectable levels of cytokines in NOD glands. VIP acting on NOD macrophages treated with lipopolysaccharide promoted anti-inflammatory effects by inhibiting nitric oxide synthase induction as well as IL-12 and TNF-alpha production, while stimulating IL-10. Here we present evidence on the ability of apoptotic acinar cells from submandibular glands of NOD mice to stimulate nitric oxide in both peritoneal and glandular macrophage pools to a similar extent as lipopolysaccharide + IFN-gamma. VIP was not effective to prevent nitrite accumulation and modestly increased IL-10 levels in macrophages coincubated with acinar cells. An enhanced nitrite response of NOD glandular macrophages in basal and stimulated conditions compared to peritoneal cells is also shown.
Calafat
Mario
M
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.
Larocca
Luciana
L
Roca
Valeria
V
Pérez Leirós
Claudia
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000276:immunology; D005260:Female; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology*; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology / Q000503:physiopathology; D013363:Submandibular Gland / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000494:pharmacology
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016753:Interleukin-10; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D007371:Interferon-gamma