title: Somatostatin modulates mast cell-induced responses in murine spinal neurons and satellite cells.
abstract: The course of intestinal inflammatory responses is tightly coordinated by the extensive communication between the immune system and the enteric nervous system, among which the bidirectional mast cell-neuron interaction within the intestinal wall plays a prominent role. Recent research suggests that somatostatin (SOM) is able to inhibit this self-reinforcing network by simultaneously suppressing the inflammatory activities of both neurons and mast cells. Therefore, we assessed the modulatory effects of SOM on both the short-term and long-term effects induced by the main mast cell mediators histamine (HIS) and 5-HT on spinal sensory neurons. Short-term incubation of dorsal root ganglion cultures with HIS and 5-HT induced neuronal CGRP-release and calcium-mediated activation of both neurons and nonneuronal cells, both of which effects were significantly reduced by SOM. In addition, SOM was also able to suppress the increased neuronal expression of pro- and anti-inflammatory peptides induced by long-term exposure to HIS and 5-HT. Immunocytochemical and molecular-biological experiments revealed the possible involvement of somatostatin receptor 1 (SSTR1) and SSTR2A in these profound SOM-dependent effects. These data, combined with the increased expression of pro- and anti-inflammatory peptides and several SSTRs in murine dorsal root ganglia following intestinal inflammation, reveal that intestinal inflammation not only induces the onset of proinflammatory cascades but simultaneously triggers endogenous systems destined to prevent excessive tissue damage. Moreover, these data provide for the first time functional evidence that SOM is able to directly modulate intestinal inflammatory responses by interference with the coordinating mast cell-neuron communication.
authors.affiliation: Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Joeri
authors.initials: J
authors.lastname: Van Op den bosch
authors.forename: Luc
authors.initials: L
authors.lastname: Van Nassauw
authors.forename: Eric
authors.initials: E
authors.lastname: Van Marck
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000378:metabolism* / Q000469:parasitology; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000469:parasitology; D006632:Histamine / Q000378:metabolism; D007079:Ileitis / Q000378:metabolism* / Q000469:parasitology / Q000517:prevention & control; D007082:Ileum / Q000294:innervation* / Q000469:parasitology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D027161:Satellite Cells, Perineuronal / Q000378:metabolism* / Q000469:parasitology; D012550:Schistosoma mansoni; D012701:Serotonin / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D012701:Serotonin; D013373:Substance P; D013004:Somatostatin; D006632:Histamine; C093733:somatostatin receptor 2; D015740:Calcitonin Gene-Related Peptide