Induction of alkaline phosphatase in the inflamed intestine: a novel pharmacological target for inflammatory bowel disease.
This study demonstrates the upregulation of alkaline phosphatase and the mechanisms involved in experimental colitis. All models of ileal and colonic inflammation examined, which were characterized by significant oxidative stress and neutrophil infiltration, resulted in an increase in alkaline phosphatase activity which was attributable to both epithelial cells and cells of the lamina propria, mainly leukocytes. The increase in alkaline phosphatase sensitivity to the inhibitors levamisole and homoarginine, together with changes in the apparent molecular size and in the sialization of the enzyme, indicated a change in the isoform expressed. An increase in tissue non-specific alkaline phosphatase expression was observed by Western blotting. Treatment with the bone/kidney alkaline phosphatase inhibitor levamisole or a monoclonal antibody resulted in significant protection from colonic inflammation. Taken together, these results indicate that the kidney isoform is a marker of intestinal inflammation and that it might even constitute a target for pharmacological intervention.
Sánchez de Medina
Fermín
F
Department of Pharmacology, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain. fasanchez@ugr.es
Martínez-Augustin
Olga
O
González
Raquel
R
Ballester
Isabel
I
Nieto
Ana
A
Gálvez
Julio
J
Zarzuelo
Antonio
A
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000276:immunology; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000201:enzymology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology; D007422:Intestines / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D007978:Levamisole / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D007978:Levamisole; D000469:Alkaline Phosphatase