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Open Access Publications from the University of California

Urocortins and CRF receptor type 2 variants in the male rat colon: gene expression and regulation by endotoxin and anti-inflammatory effect

  • Author(s): Yuan, P-Q
  • Wu, SV
  • Pothoulakis, C
  • Tache, Y
  • et al.

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Urocortin 1, 2 and 3 (Ucns) and corticotropin releasing factor receptor 2 (CRF2) are prominently expressed in various layers of the upper gut while current knowledge of their expression and regulation in the colonic layers are limited. We investigated Ucns and CRF2 isoforms expression by RT-PCR in the proximal colon separated into mucosa and submucosa plus muscle (S+M), or in laser captured layers, their regulations by lipopolysaccharide (LPS, 100 μg/kg ip) and the effects of the CRF2 antagonist astresssin2-B on colonic immune response to LPS in rats. Transcripts of Ucns and CRF2b, the most common wild-type isoform in the periphery, were detected in all layers including myenteric neurons. LPS increased Ucn 1, Ucn 2 or Ucn 3 mRNA and decreased CRF2b mRNA levels in both colonic mucosa and S+M layers at 2, 6, 9 h after injection with a return to the basal level at 24 h. In addition, CRF2a, another wild-type isoform more prominently in the CNS, and a novel truncated splice variant CRF2a-3 were detected in the large intestine. LPS reciprocally regulated these CRF2 variants by decreasing both CRF2a and CRF2b, while increasing CRF2a-3 in the mucosa and S+M of colon. Astressin2-B further enhanced LPS-induced interleukin-1β, tumor necrosis factor-α in both colonic layers and inducible nitric oxide synthase mRNA levels in S+M layers. These data indicate that Ucns/CRF2 are widely expressed in rat colonic layers, and reciprocally regulated by LPS and that CRF2 signaling dampens the CD14/TLR4 mediated acute inflammatory response to Gram negative bacteria in the colon.

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