Expression and Activation of NF-κB in the Antrum of the Human Stomach

Brink, Gijs R. van den; Kate, Fiebo J. ten; Ponsioen, Cyriel Y.; Rive, Maria M.; Tytgat, G. N. J.; Deventer, Sander J. van; Peppelenbosch, Maikel P.

doi:10.4049/jimmunol.164.6.3353

Cited by 80 publications

(50 citation statements)

References 36 publications

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“…The mechanisms and signaling pathways involved in H. pylori induction of NF-B responses in human GECs have been studied in great detail in vitro, yet the in vivo relevance of these observations has only rarely been investigated. Activated NF-B complexes were detected by immunohistochemistry within the gastric mucosa of individuals chronically infected with H. pylori (17,18,46). Consistent with the work presented here (Fig.…”

Section: Vol 76 2008 Helicobacter-induced Nf-b Activation In Mice 557supporting

confidence: 88%

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NF-κB Activation during AcuteHelicobacter pyloriInfection in Mice

Ferrero¹,

Avé²,

Ndiaye

et al. 2008

Infect Immun

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Nuclear factor B (NF-B) plays a key regulatory role in host cell responses to Helicobacter pylori infection in humans. Although mice are routinely used as a model to study H. pylori pathogenesis, the role of NF-B in murine cell responses to helicobacters has not been studied in detail. We thus investigated the abilities of different Helicobacter isolates to induce NF-B-dependent responses in murine gastric epithelial cells (GECs) and in transgenic mice harboring an NF-B-responsive lacZ reporter gene. H. pylori and Helicobacter felis strains up-regulated the synthesis in mouse GECs of the NF-B-dependent chemokines KC (CXCL1) and MIP-2 (CXCL2). These responses were cag pathogenicity island (cagPAI) independent and could be abolished by pretreatment with a pharmacological inhibitor of NF-B. Consistent with the in vitro data, experimental Helicobacter infection of transgenic mice resulted in increased numbers of GECs with nuclear ␤-galactosidase activity, which is indicative of specific NF-B activation. The numbers of ␤-galactosidase-positive cells in mice were significantly increased at day 1 postinoculation with wild-type H. pylori strains harboring or not harboring a functional cagPAI, compared to naive animals (P ‫؍‬ 0.007 and P ‫؍‬ 0.04, respectively). Strikingly, however, no differences were observed in the levels of gastric NF-B activation at day 1 postinoculation with H. felis or at day 30 or 135 postinoculation with H. pylori. This work demonstrates for the first time the induction of NF-B activation within gastric mucosal cells during acute H. pylori infection. Furthermore, the data suggest that helicobacters may be able to regulate NF-B signaling during chronic infection.

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Section: Vol 76 2008 Helicobacter-induced Nf-b Activation In Mice 557supporting

confidence: 88%

“…pylori has been shown to up-regulate the expression of the transcription factor nuclear factor B (NF-B) in gastric epithelial cells (GECs) in vitro (21), as well as during chronic infection in humans (17,46). NF-B is a key regulator of proinflammatory responses in host cells (15).…”

mentioning

confidence: 99%

NF-κB Activation during AcuteHelicobacter pyloriInfection in Mice

Ferrero¹,

Avé²,

Ndiaye

et al. 2008

Infect Immun

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“…The same anti active NF-kB antibody has been used to perform immunohistochemistry in formalin ®xed, para n embedded tissue in other studies including several that have shown activated NF-kB in macrophages (Gaweco et al, 2000;Rogler et al, 1998). We ourselves have previously shown the speci®city of this antibody under the same conditions by showing colocalisation of TNFa, TRAF-2 and total NF-kB staining with the active NF-kB staining and showing clear nuclear localisation of the active NF-kB (van Den Brink et al, 2000). Phosphospeci®c antibodies are also increasingly being used in immunohistochemistry in formalin ®xed, para n embedded tissue, especially pJNK and pp38 MAPK (Omori et al, 2000;Pirvola et al, 2000).…”

Section: Discussionmentioning

confidence: 92%

NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps

et al. 2001

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The factors that govern the progression from colonic adenomatous polyp to colon cancer are poorly understood. The observation that NSAIDs act as chemopreventative agents and reduce the size of colonic polyps suggests the involvement of in¯ammatory signalling, but in¯ammatory signalling in colonic polyps has not been studied. We investigated the expression of the active forms of NF-kB, JNK and p38 MAPK using immunohistochemistry with activation speci®c antibodies in human colonic adenomas. We show that active NF-kB is seen in stromal macrophages that also express COX-2 and TNF-a, active JNK is seen in stromal and intraepithelial T-lymphocytes and periendothelial cells of new blood vessels, and active p38 MAPK is most highly expressed in macrophages and other stromal cells. These results demonstrate the presence of active in¯ammatory signal transduction in colonic polyps and that these are predominantly in the stroma. In the case of NF-kB this coincides with the cellular localisation of COX-2. These results support evidence that NSAIDs may act through e ects on stromal cells rather than epithelial cells. Oncogene (2001) 20, 819 ± 827.

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“…Helicobacter pylori-associated gastritis is also marked by increased NF-κB activity in gastric epithelial cells (38). The number of NF-κB positive cells correlates with the degree of gastritis.…”

Section: Nf-κb Activation In Human Inflammatory Diseasesmentioning

confidence: 99%