Expressions of tight junction proteins and interleukin-6 in mucosa of reflux esophagitis

Abstract

Objective To investigate the distribution and expression of tight junction proteins (including elaudin 1, occludin,ZO-1 and JAM-1) in mucosa of rats with reflux esophagitis (RE), and its underline mechanism in pathogenesis of RE. Methods Two hundred and twenty 8-week-old male Wistar rats were divided into sham operation control group (n=10), acid reflux group (n=70), alkaline reflux group (n=70) and mixed reflux group (n=70). The rats were sacrificed at day 3, 6, 9 and 14 after operation. The successful rate of modeling was assessed by evidence of inflammation in middle and low esophagus. Transmission electron microscopy (TEM) was used to observe the morphological changes of tight junction in esophageal epithelium. The mRNA and protein expressions of tight junction proteins were detected by Western blotting and RT-PCR, respectively. And interleukin (IL)-6 expression was measured by immunohistochemistry. Results At day 14 after the procedure, RE model was established in all executed rats. Successful rate of 100% was achieved. The microscopic observation showed that mucosa was damaged and thickened as the disease progressed. With TEM observation, widened intercellular space was noticed with fewer desmosomes. Elevated expressions of IL-6 and tight junction proteins were found in three model groups compared with control group. Whereas the expression of tight junction proteins in individual cells was gradually decreased with continuing hyperplasia in the basal layer. The mRNA and protein expressions of IL-6 and tight junction proteins were increased gradually as disease progressed. Conclusions The highly expression of tight junction proteins, which involves in the mechanism of RE by playing the role of positive regulation and synergism, may be early molecular event in development of RE. And IL-6 is an inflammatory factor in this process. Key words: Esophagitis; Tight junctions; Interleukin-6