A new mechanism for anti‐inflammatory actions of proton pump inhibitors – inhibitory effects on neutrophil–endothelial cell interactions

Abstract

Background: Neutrophil±endothelial cell interactions mediated by adhesion molecules may be involved in gastric mucosal in¯ammation associated with Helicobacter pylori or nonsteroidal anti-in¯ammatory drugs. Aim: To investigate the effects of proton pump inhibitors and histamine-2 receptor antagonists (HRA) on neutrophil-endothelial cell adhesive interactions induced by H. pylori water extract (HPE) or interleukin-1b (IL-1b). Methods: Human peripheral neutrophils and umbilical vein endothelial cells were incubated with either proton pump inhibitors (lansoprazole and omeprazole) or HRA (famotidine and ranitidine). Neutrophil surface expression of CD11b and CD18 and endothelial cell intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were assessed by¯ow cytometry and an enzyme immunoassay,

Present status and strategy of NSAIDs-induced small bowel injury

“…PPI is also known to have protective effects on gastrointestinal mucosa without the inhibition of acid secretion [58][59][60]. Such protective effects have been reported to occur via anti-inflammatory effects such as the inhibition of IL-8 production and neutrophil infiltration and via cell injury repair through MAPK [61][62][63]. The previous studies also found that lansoprazole reduced NSAID-induced small-intestinal mucosal injuries as in our study [64,65].…”

The Expression of Heme Oxygenase-1 Induced by Lansoprazole

“…In addition to its acid-suppressing effects, lansoprazole have been shown to modulate the inflammatory status, reduce oxidative stress, and ameliorate mucosal injuries in the esophagus [23,24], intestine [25,26], and lung [27], in addition to the stomach [28,29]. It has been also demonstrated by in vitro studies that lansoprazole inhibits the increased expression of vascular adhesion molecules, the activation of neutrophils, and the production of pro-inflammatory cytokines from activated endothelial cells [30,31]. We recently demonstrated using in vivo models that lansoprazole inhibits acute inflammatory reactions as well as intestinal mucosal injuries induced by ischemia-reperfusion [25] or indomethacin administration in rats [26].…”

The effect of proton pump inhibitors on the gastric mucosal microenvironment

“…PPIs can attenuate neutrophil adherence to endothelial cells by inhibiting the expression of adhesion molecules. 13 The results of the current study indicated that PPIs may attenuate the infiltration of neutrophils in the gastric antral mucosa. Infiltrating neutrophils play an important role in gastric mucosal injury, particularly in regard to oxidative stress and inflammatory cytokines.…”

“…[9][10][11][12] PPIs affect the interaction of neutrophils with endothelial cells and attenuate neutrophil association with chemostatic cytokines of gastric mucosa. 2,4,13 However, the effect of PPIs on gastric mucosa and neutrophils has not been thoroughly clarified. 14,15 This study investigated the effect of PPIs on H. pylori, neutrophil infiltration and gastric antral mucosa inflammation.…”