Activation of IkappaB kinase and NF-kappaB is essential for Helicobacter pylori-induced chronic gastritis in Mongolian gerbils.
The Mongolian gerbil model of Helicobacter pylori infection resembles human gastritis. In this study, we investigated the role of NF-kappaB activation in H. pylori-infected gerbils. Activated macrophages were significantly increased in H. pylori-infected gastric mucosa and were identified as being important cells with potent activation of NF-kappaB, which plays an important part in producing proinflammatory cytokines. Macrophage depletion by the administration of clodronate resulted in milder inflammation in gerbils infected with H. pylori. In macrophages, the inhibition of IkappaB kinase beta (IKKbeta), which is a critical kinase for NF-kappaB activation, resulted in lower proinflammatory cytokine expression caused by heat-killed H. pylori cells. Furthermore, treatment with IKKbeta inhibitor resulted in milder inflammation in gerbils with H. pylori gastritis. Collectively, our data suggest that H. pylori-mediated gastric inflammation critically depends on the efficient recruitment and activation of macrophages, with sufficient NF-kappaB activation.
Yanai
Ayako
A
Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Tokyo 100-0005, Japan.
Maeda
Shin
S
Shibata
Wataru
W
Hikiba
Yohko
Y
Sakamoto
Kei
K
Nakagawa
Hayato
H
Ohmae
Tomoya
T
Hirata
Yoshihiro
Y
Ogura
Keiji
K
Muto
Susumu
S
Itai
Akiko
A
Omata
Masao
M
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005753:Gastric Mucosa / Q000473:pathology; D005756:Gastritis / Q000382:microbiology* / Q000473:pathology*; D005849:Gerbillinae; D016480:Helicobacter pylori / Q000502:physiology*; D051550:I-kappa B Kinase / Q000378:metabolism*; D047589:Leukocyte Reduction Procedures; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*
D016207:Cytokines; D016328:NF-kappa B; D051550:I-kappa B Kinase