The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells
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 acin...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/3745961 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849685954768404480 |
|---|---|
| author | Dong Un Lee Dong Min Shin Jeong Hee Hong |
| author_facet | Dong Un Lee Dong Min Shin Jeong Hee Hong |
| author_sort | Dong Un Lee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bac64d7fcde8458aad5b553fa3af5657 |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-bac64d7fcde8458aad5b553fa3af56572025-08-20T03:22:53ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/37459613745961The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland CellsDong Un Lee0Dong Min Shin1Jeong Hee Hong2Department of Physiology, College of Medicine, Gachon University, 191 Hambakmeoro, Yeonsu-gu, Incheon 406-799, Republic of KoreaDepartment of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 120-752, Republic of KoreaDepartment of Physiology, College of Medicine, Gachon University, 191 Hambakmeoro, Yeonsu-gu, Incheon 406-799, Republic of KoreaExposure 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.http://dx.doi.org/10.1155/2016/3745961 |
| spellingShingle | Dong Un Lee Dong Min Shin Jeong Hee Hong The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells Mediators of Inflammation |
| title | The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells |
| title_full | The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells |
| title_fullStr | The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells |
| title_full_unstemmed | The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells |
| title_short | The Regulatory Role of Rolipram on Inflammatory Mediators and Cholinergic/Adrenergic Stimulation-Induced Signals in Isolated Primary Mouse Submandibular Gland Cells |
| title_sort | regulatory role of rolipram on inflammatory mediators and cholinergic adrenergic stimulation induced signals in isolated primary mouse submandibular gland cells |
| url | http://dx.doi.org/10.1155/2016/3745961 |
| work_keys_str_mv | AT dongunlee theregulatoryroleofrolipramoninflammatorymediatorsandcholinergicadrenergicstimulationinducedsignalsinisolatedprimarymousesubmandibularglandcells AT dongminshin theregulatoryroleofrolipramoninflammatorymediatorsandcholinergicadrenergicstimulationinducedsignalsinisolatedprimarymousesubmandibularglandcells AT jeongheehong theregulatoryroleofrolipramoninflammatorymediatorsandcholinergicadrenergicstimulationinducedsignalsinisolatedprimarymousesubmandibularglandcells AT dongunlee regulatoryroleofrolipramoninflammatorymediatorsandcholinergicadrenergicstimulationinducedsignalsinisolatedprimarymousesubmandibularglandcells AT dongminshin regulatoryroleofrolipramoninflammatorymediatorsandcholinergicadrenergicstimulationinducedsignalsinisolatedprimarymousesubmandibularglandcells AT jeongheehong regulatoryroleofrolipramoninflammatorymediatorsandcholinergicadrenergicstimulationinducedsignalsinisolatedprimarymousesubmandibularglandcells |