Angiotensin II-generating enzymes, angiotensin-converting enzyme (ACE) and mast cell chymase (CMA1), in gastric inflammation may be regulated by H. pylori and associated cytokines.
BACKGROUND
The local angiotensin II system (LAS) has numerous functions, including the regulation of growth and differentiation in the gastrointestinal tract. Angiotensin II (AngII) may be generated by angiotensin-I-converting enzyme (ACE) or mast cell chymase (CMA1) and plays an important role in inflammatory processes, although opinions differ as to which AngII-generating enzyme is primarily associated with AngII-mediated effects. ACE inhibitors have been shown to have a protective or healing effect on gastric ulcers and colitis in animal models, which could be related to the local expression of ACE.


METHODS
The localisation of ACE and CMA1 was examined immunohistochemically in Helicobacter pylori gastritis, non-H. pylori gastritis, gastric ulcers and non-lesional gastric tissues. Using real-time qRT-PCR, ACE- and CMA1-mRNA expression in gastric cell lines were examined and changes in ACE levels after exposure to H. pylori or cytokines (IL-1beta, IL-6, IL-8, TNF, TGFbeta1) were quantified.


RESULTS
ACE and CMA1 were not expressed in the non-lesional foveolar epithelium. Cytoplasmic staining for ACE in fundic chief cells, and apical membranous expression of ACE in the mucin-secreting cells of the antral and pyloric region was observed. ACE was found in endothelial cells of the gastric ulcer granulation tissue and CMA1 was strongly expressed in mast cells. ACE but not CMA1 was expressed in the MKN28, N87 and MKN45 gastric cell lines, and ACE mRNA expression was regulated by both H. pylori and the cytokines.


CONCLUSIONS
ACE in the gastric mucosa and the microvasculature of granulation tissue may represent a novel therapeutic target for the promotion of healing processes in gastritis and ulceration using ACE inhibitors or AT1R antagonists.
Institute of Pathology, Charité University Hospital, Berlin, Germany. stacy.carl-mcgrath@charite.de
Stacy
S
Carl-McGrath
Ilona
I
Gräntzdörffer
Uwe
U
Lendeckel
Matthias P
MP
Ebert
Christoph
C
Röcken
D000804:Angiotensin II / Q000378:metabolism; D053818:Chymases / Q000096:biosynthesis*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology; D005756:Gastritis / Q000201:enzymology*; D016481:Helicobacter Infections / Q000201:enzymology; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013276:Stomach Ulcer / Q000201:enzymology*
D016207:Cytokines; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C509226:CMA1 protein, human; D053818:Chymases