Enhanced Expression of Cystathionine β-Synthase and Cystathionine γ-Lyase During Acute Cholecystitis-Induced Gallbladder Inflammation

BACKGROUND: Hydrogen sulfide (H(2)S) has recently been shown to play an important role in the digestive system, but the role of endogenous H(2)S produced locally in the gallbladder is unknown. The aim of this study was to investigate whether gallbladder possesses the enzymatic machinery to synthesize H(2)S, and whether H(2)S synthesis is changed in gallbladder inflammation during acute acalculous cholecystitis (AC). METHODS: Adult male guinea pigs underwent either a sham operation or common bile duct ligation (CBDL). One, two, or three days after CBDL, the animals were sacrificed separately. Hematoxylin and eosin-stained slides of gallbladder samples were scored for inflammation. H(2)S production rate in gallbladder tissue from each group was determined; immunohistochemistry and western blotting were used to determine expression levels of the H(2)S-producing enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in gallbladder. RESULTS: There was a progressive inflammatory response after CBDL. Immunohistochemistry analysis showed that CBS and CSE were expressed in the gallbladder epithelium, muscular layer, and blood vessels and that the expression increased progressively with increasing inflammation following CBDL. The expression of CBS protein as well as the H(2)S-production rate was significantly increased in the animals that underwent CBDL, compared to those that underwent the sham operation. CONCLUSIONS: Both CBS and CSE are expressed in gallbladder tissues. The expression of these enzymes, as well as H(2)S synthesis, was up-regulated in the context of inflammation during AC.