Effects of autonomic agonists and immunomodulatory cytokines on polymeric immunoglobulin receptor expression by cultured rat and human salivary and colonic cell lines.

OBJECTIVE: Immunoglobulin A (IgA) is transported across glandular epithelial cells by polymeric immunoglobulin receptor (plgR), with each receptor molecule participating in only one round of transcytosis. Nerve-related stimuli rapidly increase salivary secretion of IgA, while concentrations are increased in the autoimmune disease Sjögren's syndrome. Our aim here was to determine whether autonomic agonists and cytokines present in Sjögren's-affected glands can up-regulate salivary cell plgR expression. METHODS: Cultures of rat parotid acinar cells (PAR C5) and human submandibular gland ductal cells (HSG) were exposed to carbachol or adrenaline for 24 h and to interleukin-4 and/or interferon-gamma for 48 h. The human colonic cell line HT-29 served as a positive control for cytokine response. plgR mRNA was quantified by reverse transcription and real-time PCR and protein expression was examined by immunoblotting. RESULTS: Carbachol increased plgR mRNA levels significantly in all cells but adrenaline did so only with PAR cells (P<0.05). HSG and HT-29 cells both up-regulated plgR gene transcription on exposure to interleukin-4 and interferon-gamma either alone or in combination (P<0.05). By contrast, production of plgR mRNA in PAR cells tended to decrease in response to all cytokine treatments. plgR protein levels rose in line with mRNA expression in cytokine-treated HT-29 cultures (P<0.05). CONCLUSIONS: Autonomimetics can up-regulate plgR transcription in transformed and neoplastic salivary and colonic cells, although intracellular coupling mechanisms require further investigation. Immunomodulatory cytokines increased plgR expression in one of the salivary cell lines, but additional work is needed to establish whether this occurs in Sjögren's patients.

Salivary secretion of immunoglobulin A by submandibular glands in response to autonomimetic infusions in anaesthetised rats.

Salivary secretion of immunoglobulin A (lgA) by submandibular glands is increased by stimuli from autonomic nerves. Since it is unclear which specific autonomic receptors transduce such stimuli, we have infused autonomimetics intravenously and compared secretion of fluid, IgA and stored proteins (peroxidase and total protein) with secretory responses during electrical stimulation of the parasympathetic nerve supply in anaesthetized rats. The greatest secretion of IgA was evoked by the alpha-adrenoceptor agonist phenylephrine and this was reduced by the beta-adrenoceptor blocking drug propranolol. The secretion of fluid or proteins but not IgA was increased with frequency of nerve stimulation and dose of methacholine (cholinergic), isoprenaline (beta-adrenergic) or phenylephrine (alpha-adrenergic).