Proton pump inhibitors exert anti-allergic effects by reducing TCTP secretion.
BACKGROUND
Extracellular translationally controlled tumor protein (TCTP) is known to play a role in human allergic responses. TCTP has been identified outside of macrophages, in activated mononuclear cells, and in biological fluids from allergic patients. Even TCTP devoid of signal sequences, is secreted to extracellular environment by an yet undefined mechanism. This study is aimed at understanding the mechanism of TCTP release and its regulation. A secondary goal is to see if inhibitors of TCTP release can serve as potential anti-allergic asthmatic drugs.


RESULTS
Using Western blotting assay in HEK293 and U937 cells, we found that TCTP secretion is reduced by omeprazole and pantoprazole, both of which are proton pump inhibitors. We then transfected HEK293 cells with proton pump expression vectors to search for the effects of exogeneously overexpressed H(+)/K(+)-ATPase on the TCTP secretion. Based on these in vitro data we checked the in vivo effects of pantoprazole in a murine model of ovalbumin-induced allergy. Omeprazole and pantoprazole reduced TCTP secretion from HEK293 and U937 cells in a concentration-dependent fashion and the secretion of TCTP from HEK293 cells increased when they over-expressed H(+)/K(+)-ATPase. In a murine model of ovalbumin-induced allergy, pretreatment with pantoprazole reduced infiltration of inflammatory cells, increased goblet cells, and increased TCTP secretion induced by OVA challenge.


CONCLUSIONS
Since Omeprazole and pantoprazole decrease the secretion of TCTP which is associated with the development of allergic reaction, they may have the potential to serve as anti-allergic (asthmatic) drugs.
Choi
Sunghee
S
College of Pharmacy, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
Min
Hyun Jung
HJ
Kim
Miyoung
M
Hwang
Eun Sook
ES
Lee
Kyunglim
K
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism* / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid; D006801:Humans; D006967:Hypersensitivity; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000077402:Pantoprazole; D010957:Plasmids / Q000378:metabolism; D017494:Proton Pumps / Q000378:metabolism*; D000090324:Tumor Protein, Translationally-Controlled 1; D020298:U937 Cells
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D018926:Anti-Allergic Agents; D000897:Anti-Ulcer Agents; D014408:Biomarkers, Tumor; D017494:Proton Pumps; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D000077402:Pantoprazole