Somatostatin inhibits dendritic cell responsiveness to Helicobacter pylori.
Somatostatin is a regulatory peptide found in abundance in the stomach. We have previously shown that somatostatin is required for IL-4-mediated resolution of Helicobacter pylori gastritis. In the current study, we hypothesize that somatostatin acts directly on antigen-presenting cells in the stomach to lessen the severity of gastritis. To test this hypothesis, we first show that CD11c+ dendritic cells are present in the infected tissue of mice with H. pylori-induced gastritis. Pretreatment of bone marrow-derived dendritic cells with somatostatin results in decreased IL-12 production, and lower splenocyte proliferation induced by H. pylori-stimulated dendritic cells. Furthermore, octreotide, a somatostatin analogue, is more potent than somatostatin in suppressing IL-12 release by H. pylori-stimulated dendritic cells through an NF-kappaB-independent pathway. In addition, IL-4 stimulates somatostatin secretion from dendritic cells. In conclusion, somatostatin inhibits dendritic cell activation by H. pylori; a possible mechanism by which IL-4 mediates resolution of gastritis. We suggest that octreotide may be effective in treating immune-mediated diseases of the stomach.
Kao
John Y
JY
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 6520A MSRB 1, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0650, USA. jykao@umich.edu
Pierzchala
Anna
A
Rathinavelu
Sivaprakash
S
Zavros
Yana
Y
Tessier
Arthur
A
Merchant
Juanita L
JL
D021581:Active Transport, Cell Nucleus; D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000276:immunology / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism / Q000472:pathogenicity*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D015282:Octreotide / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism; D013270:Stomach / Q000473:pathology
D016207:Cytokines; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4; D013004:Somatostatin; D015282:Octreotide