title: The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells.
abstract: 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 Ca(2+) 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 Ca(2+) signaling and ROS production in SMG. Treatment with rolipram blocked LPS-induced Ca(2+) increase and ROS production. The application of histamine evoked Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Department of Physiology, College of Medicine, Gachon University, 191 Hambakmeoro, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Dong Un
authors.initials: DU
authors.lastname: Lee
authors.affiliation: Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea.
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Shin
authors.affiliation: Department of Physiology, College of Medicine, Gachon University, 191 Hambakmeoro, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020889:Rolipram / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013363:Submandibular Gland / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D006632:Histamine; D020889:Rolipram