Sphingosine-1-phosphate signaling in human submandibular cells.
Sphingosine-1-phosphate (S1P) is a significant lipid messenger modulating many physiological responses. S1P plays a critical role in autoimmune disease and is suggested to be involved in Sjögren's syndrome pathology. However, the mechanism of S1P signaling in salivary glands is unclear. Here we studied the effects of S1P on normal human submandibular gland cells. S1P increased levels of the intracellular Ca(2+) concentration ([Ca(2+)](i)), which was inhibited by pre-treatment with U73122 or 2-aminoethoxydiphenyl borate (2-APB). Pre-treated S1P did not inhibit subsequent carbachol-induced [Ca(2+)](i) increase, which suggests that S1P and muscarinic signaling are independent of each other. S1P1, S1P2, and S1P3 receptors SphK1 and SphK2 were commonly expressed in human salivary gland cells. S1P, but not carbachol, induces the expression of interleukin-6 and Fas. Our results suggest that S1P triggers Ca(2+) signaling and the apoptotic pathway in normal submandibular gland cells, which suggests in turn that S1P affects the progression of Sjögren's syndrome.
Seo
J
J
Department of Physiology, Institute of Medical Science, Kangwon National University School of Medicine, Chuncheon 200-701, Korea.
Koo
N Y
NY
Choi
W Y
WY
Kang
J A
JA
Min
J H
JH
Jo
S H
SH
Lee
S J
SJ
Oh
S B
SB
Kim
J S
JS
Lee
J H
JH
Choi
S Y
SY
Park
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D001896:Boron Compounds / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000032:analysis; D011760:Pyrrolidinones / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012859:Sjogren's Syndrome / Q000503:physiopathology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000502:physiology; D013363:Submandibular Gland / Q000166:cytology* / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D019014:fas Receptor / Q000187:drug effects; D000099157:Sphingosine Kinase
D001896:Boron Compounds; D002217:Carbachol; D018679:Cholinergic Agonists; D004963:Estrenes; D015850:Interleukin-6; D008246:Lysophospholipids; D010726:Phosphodiesterase Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D011760:Pyrrolidinones; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D010738:Type C Phospholipases; D019014:fas Receptor; D000099157:Sphingosine Kinase; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C060506:sphingosine 1-phosphate; C109986:2-aminoethoxydiphenyl borate