The Regulatory Role of Rolipram on Inflammatory Mediators and CholinergicAdrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells

Abstract EN

Exposure to bacterial lipopolysaccharides (LPS) induces inflammatory signals in salivary glands.

We investigated the regulatory role of phosphodiesterase 4 (PDE4) inhibitor rolipram on inflammatory mediators and cholinergic/adrenergic stimulation-induced intracellular Ca2+ signaling in salivary acinar and ductal cells.

Submandibular gland (SMG) expressed PDE4A through 4D mRNA and PDE4 was localized in the luminal membrane of SMG.

LPS induced Ca2+ signaling and ROS production in SMG.

Treatment with rolipram blocked LPS-induced Ca2+ increase and ROS production.

The application of histamine evoked Ca2+ signals and ROS production, which were attenuated by rolipram in SMG cells.

Moreover, LPS-induced NLRP3 inflammasome and cleaved caspase-1 were inhibited by rolipram.

The inhibitory role of rolipram in ROS-induced Ca2+ signaling was mainly observed in acinar cells and not in ductal cells.

Rolipram also protected SMG acinar but not ductal cells from LPS-induced cell membrane damage.

In the case of cholinergic/adrenergic stimulation, carbachol/isoproterenol-induced Ca2+ signals were upregulated by the treatment of rolipram in SMG.

In the case of cAMP-dependent ductal bicarbonate secretion by rolipram, no effect was observed on the modulation of ductal chloride/bicarbonate exchange activity.

Rolipram could suppress the inflammatory signals and could be a potential therapeutic strategy against LPS-induced inflammation to protect the salivary gland cells.