Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection
We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2 − / − mice exhibited increased NOS2 levels in gastr...
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Published in | Amino acids Vol. 48; no. 10; pp. 2375 - 2388 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Vienna
Springer Vienna
01.10.2016
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during
Helicobacter pylori
infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as
Arg2
−
/
−
mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill
H. pylori
. We now bred
Arg2
−
/
−
to
Nos2
−
/
−
mice, and infected them with
H. pylori
. Compared to wild-type mice, both
Arg2
−
/
−
and
Arg2
−
/
−
;Nos2
−
/
−
mice exhibited increased gastritis and decreased colonization, the latter indicating that the effect of ARG2 deletion on bacterial burden was not mediated by NO. While
Arg2
−
/
−
mice demonstrated enhanced M1 macrophage activation,
Nos2
−
/
−
and
Arg2
−
/
−
;Nos2
−
/
−
mice did not demonstrate these changes, but exhibited increased CXCL1 and CXCL2 responses. There was an increased expression of the Th1/Th17 cytokines, interferon gamma and interleukin 17, in gastric tissues and splenic T-cells from
Arg2
−
/
−
, but not
Nos2
−
/
−
or
Arg2
−
/
−
;Nos2
−
/
−
mice. Gastric tissues from infected
Arg2
−
/
−
mice demonstrated increased expression of arginase 1, ornithine decarboxylase, adenosylmethionine decarboxylase 1, spermidine/spermine
N
1
-acetyltransferase 1, and spermine oxidase, along with increased spermine levels. These data indicate that ARG2 deletion results in compensatory upregulation of gastric polyamine synthesis and catabolism during
H. pylori
infection, which may contribute to increased gastric inflammation and associated decreased bacterial load. Overall, the finding of this study is that ARG2 contributes to the immune evasion of
H. pylori
by restricting M1 macrophage activation and polyamine metabolism. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0939-4451 1438-2199 |
DOI: | 10.1007/s00726-016-2231-2 |