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

Authors
 Dong Un Lee  ;  Dong Min Shin  ;  Jeong Hee Hong 
Citation
 MEDIATORS OF INFLAMMATION, Vol.2016 : 3745961, 2016 
Journal Title
 MEDIATORS OF INFLAMMATION 
ISSN
 0962-9351 
Issue Date
2016
MeSH
Animals ; Calcium Signaling/drug effects ; Cells, Cultured ; Histamine/pharmacology ; Inflammation/metabolism* ; Lipopolysaccharides/pharmacology ; Mice ; Reactive Oxygen Species/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rolipram/pharmacology* ; Signal Transduction/drug effects ; Submandibular Gland/drug effects* ; Submandibular Gland/metabolism*
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.
Files in This Item:
T201600996.pdf Download
DOI
10.1155/2016/3745961
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146626
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