HCl-induced inflammatory mediators in cat esophageal mucosa and inflammatory mediators in esophageal circular muscle in an in vitro model of esophagitis.
Platelet-activating factor (PAF) and interleukin-6 (IL-6) are produced in the esophagus in response to HCl and affect ACh release, causing changes in esophageal motor function similar to esophagitis (Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, and Harnett KM. Am J Physiol Gastrointest Liver Physiol 289: G418-G428, 2005). We therefore examined HCl-activated mechanisms for production of PAF and IL-6 in cat esophageal mucosa and circular muscle. A segment of normal mucosa was tied at both ends, forming a mucosal sac (Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, and Harnett KM. Am J Physiol Gastrointest Liver Physiol 289: G860-G869, 2005) that was filled with acidic Krebs buffer (pH 5.8) or normal Krebs buffer (pH 7.0) as control and kept in oxygenated Krebs buffer for 3 h. The supernatant of the acidic sac (MS-HCl) abolished contraction of normal muscle strips in response to electric field stimulation. The inhibition was reversed by the PAF antagonist CV3988 and by IL-6 antibodies. PAF and IL-6 levels in MS-HCl and mucosa were significantly elevated over control. IL-6 levels in mucosa and supernatant were reduced by CV3988, suggesting that formation of IL-6 depends on PAF. PAF-receptor mRNA levels were not detected by RT-PCR in normal mucosa, but were significantly elevated after exposure to HCl, indicating that HCl causes production of PAF and expression of PAF receptors in esophageal mucosa and that PAF causes production of IL-6. PAF and IL-6, produced in the mucosa, are released to affect the circular muscle layer. In the circular muscle, PAF causes production of additional IL-6 that activates NADPH oxidase to induce production of H(2)O(2). H(2)O(2) causes formation of IL-1beta that may induce production of PAF in the muscle, possibly closing a self-sustaining cycle of production of inflammatory mediators.
Cheng
Ling
L
Department of Medicine, Rhode Island Hospital and Brown University, Providence, 02903, USA.
Cao
Weibiao
W
Fiocchi
Claudio
C
Behar
Jose
J
Biancani
Piero
P
Harnett
Karen M
KM
D000818:Animals; D002415:Cats; D004195:Disease Models, Animal; D004941:Esophagitis / Q000139:chemically induced / Q000276:immunology*; D004947:Esophagus / Q000187:drug effects / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000276:immunology*; D010666:Phenylpropionates; D017382:Reactive Oxygen Species / Q000276:immunology
D018836:Inflammation Mediators; D010666:Phenylpropionates; D017382:Reactive Oxygen Species; C035253:3-phenylpropionic acid