Role of ASC in the mouse model of Helicobacter pylori infection.
Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) is an adaptor molecule activating caspase-1 that stimulates pro-interleukin-1beta (pro-IL-1beta) and pro-IL-18, two pro-inflammatory cytokines with critical functions in host defense against a variety of pathogens. In this study, we investigated the role of ASC in the host defense against Helicobacter pylori utilizing ASC-deficient mice. Mice were orally inoculated with H. pylori; bacterial load, degree of gastritis, and mucosal levels of inflammatory cytokines were analyzed and compared with those obtained from wild-type mice. We found more prominent H. pylori colonization in ASC-deficient mice, as revealed by colony-forming unit counts. Both groups of mice developed gastritis; however, ASC-deficient mice showed significant attenuation of inflammation despite high H. pylori colonization. ELISA, immunohistochemistry, and quantitative RT-PCR analyses revealed complete suppression of IL-1beta and IL-18, and substantial reduction of interferon-gamma (IFN-gamma) expression, in ASC-deficient mice without apparent upregulation of other cytokines, including IL-10 and tumor necrosis factor-alpha. These results as a whole indicate that ASC exerts considerable influence on the host defense, acting through IL-1beta/IL-18 and subsequent IFN-gamma production, which in turn contributes to continuous chronic inflammatory response and consequent reduction of H. pylori colonization.
Benoit
Bekale N
BN
Department of Molecular Oncology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Kobayashi
Motohiro
M
Kawakubo
Masatomo
M
Takeoka
Michiko
M
Sano
Kenji
K
Zou
Jian
J
Itano
Naoki
N
Tsutsui
Hiroko
H
Noda
Tetsuo
T
Fukuda
Minoru
M
Nakayama
Jun
J
Taniguchi
Shun'ichiro
S
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; C498534:Pycard protein, mouse; D007371:Interferon-gamma