In vitro model of acute esophagitis in the cat.
We have shown that IL-1beta and IL-6, possibly originating from the mucosa in response to injury, inhibit neurally mediated contraction of esophageal circular muscle but do not affect ACh-induced contraction, reproducing the effect of experimental esophagitis on esophageal contraction. To examine the interaction of mucosa and circular muscle in inflammation, we examined the effect of HCl on in vitro esophageal mucosa and circular muscle. Circular muscle strips, when directly exposed to HCl, contracted normally. However, when circular muscle strips were exposed to supernatants of mucosa incubated in HCl (2-3 h, pH 5.8), contraction decreased, and the inhibition was partially reversed by an IL-6 antibody. Supernatants from the mucosa of animals with in vivo-induced acute esophagitis (AE) similarly reduced contraction. IL-6 levels were higher in mucosal tissue from AE animals than in control mucosa and in AE mucosa supernatants than in normal mucosa supernatants. IL-6 levels increased significantly in normal mucosa and supernatants in response to HCl, suggesting increased production and release of IL-6 by the mucosa. IL-6 increased H2O2 levels in the circular muscle layer but not in mucosa. Exposure of the mucosa to HCl caused IL-1beta to increase only in the mucosa and not in the supernatant. These data suggest that HCl-induced damage occurs first in the mucosa, leading to the production of IL-1beta and IL-6 but not H2O2. IL-1beta appears to remain in the mucosa. In contrast, IL-6 is produced and released by the mucosa, eventually resulting in the production of H2O2 by the circular muscle, with this affecting circular muscle contraction.
Cheng
Ling
L
Division of Gastroenterology, Rhode Island Hospital and Brown University, Providence, RI 02903, USA.
Cao
Weibiao
W
Fiocchi
Claudio
C
Behar
Jose
J
Biancani
Piero
P
Harnett
Karen M
KM
D000208:Acute Disease; D000818:Animals; D002415:Cats; D002470:Cell Survival; D004195:Disease Models, Animal; D004941:Esophagitis / Q000378:metabolism* / Q000473:pathology*; D006851:Hydrochloric Acid / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D006861:Hydrogen Peroxide; D006851:Hydrochloric Acid