IFN-γsynergizes with TNF-αbut not with viableH. pyloriin up-regulating CXC chemokine secretion in gastric epithelial cells

Kraft, Matthias; Riedel, Susanne; Kucharzik, Torsten; Steinbuechel, A.; Domschke, W; Luegering, Norbert

doi:10.1046/j.1365-2249.2001.01634.x

Cited by 38 publications

(36 citation statements)

References 37 publications

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“…Costimulation with H. pylori and IFN-g augmented IP-10 production in all cell lines, whereas stimulation with bacteria alone failed to do so ( Fig. 1B), which indicates that multiple stimuli are required for IP-10 expression in H. pylori-stimulated gastric epithelial cells, a finding consistent with that of a previous report (42). Indeed, NOD1 activation appears to be important in this regard, as IP-10 production was significantly reduced in NOD1 siRNA-treated AGS cells as compared with control cells (p , 0.0001; Fig.…”

Section: Resultssupporting

confidence: 91%

“…1, 2), indicating that multiple stimuli are required for the expression of these chemokines in gastric epithelial cells. This finding is consistent with previous studies demonstrating synergism between IFN-g and NFkB signaling pathways (42,53), but differs from the findings of a recent study, which reported robust IP-10 induction in response to a synthetic NOD1 ligand, iE-DAP (54). Further investigation is necessary to determine the mechanism of H. pylori-induced IP-10 production by gastric epithelial cells.…”

Section: Discussionsupporting

confidence: 89%

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Nucleotide Oligomerization Domain 1 Enhances IFN-γ Signaling in Gastric Epithelial Cells during Helicobacter pylori Infection and Exacerbates Disease Severity

Allison

Ferrand

McLeod

et al. 2013

The Journal of Immunology

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Virulent Helicobacter pylori strains that specifically activate signaling in epithelial cells via the innate immune molecule, nucleotide oligomerization domain 1 (NOD1), are more frequently associated with IFN-γ–dependent inflammation and with severe clinical outcomes (i.e., gastric cancer and peptic ulceration). In cell culture models, we showed that H. pylori activation of the NOD1 pathway caused enhanced proinflammatory signaling in epithelial cells in response to IFN-γ stimulation through the direct effects of H. pylori on two components of the IFN-γ signaling pathway, STAT1 and IFN regulatory factor 1 (IRF1). Specifically, H. pylori activation of the NOD1 pathway was shown to increase the levels of STAT1-Tyr701/Ser727 phosphorylation and IRF1 expression/synthesis in cells, resulting in enhanced production of the NOD1- and IFN-γ–regulated chemokines, IL-8– and IFN-γ–induced protein 10, respectively. Consistent with the notion that heightened proinflammatory signaling in epithelial cells may have an impact on disease severity, we observed significantly increased expression levels of NOD1, CXCL8, IRF1, and CXCL10 in human gastric biopsies displaying severe gastritis, when compared with those without gastritis (p < 0.05, p < 0.001, p < 0.01, and p < 0.05, respectively). Interestingly, NOD1, CXCL8, and IRF1 expression levels were also significantly upregulated in gastric tumor tissues, when compared with paired nontumor samples (p < 0.0001, p < 0.05, and p < 0.05, respectively). Thus, we propose that cross-talk between NOD1 and IFN-γ signaling pathways contribute to H. pylori–induced inflammatory responses, potentially revealing a novel mechanism whereby virulent H. pylori strains promote more severe disease.

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Section: Resultssupporting

confidence: 91%

Section: Discussionsupporting

confidence: 89%

Nucleotide Oligomerization Domain 1 Enhances IFN-γ Signaling in Gastric Epithelial Cells during Helicobacter pylori Infection and Exacerbates Disease Severity

Allison

Ferrand

McLeod

et al. 2013

The Journal of Immunology

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“…Previous studies have demonstrated that MIG expression is upregulated synergistically by stimulation with TNF-a and IFN-g indicating cytokine-regulated expression of inflammatory genes. 23,24 However, in the present study, the MIG promoter was activated by TNF-a but not by IFN-g. Although we do not know the reason why our result differed from those of the previous report cannot be explained, the mechanisms activating the MIG promoter may differ according to cellular lineage and differentiation stages.…”

Section: Discussioncontrasting

confidence: 75%

“…Moreover, IFN-g and TNF-a have been demonstrated to positively regulate the transcription of MIG gene. 23,24 As shown in Figure 3e, although IFN-g had no effect, TNF-a increased the MIG promoter activity in 293 cells when expression constructs of MUM1 and PU.1 were cotransfected.…”

Section: Mum1 Activates the Mig Promoter In Cooperation With Pu1mentioning

confidence: 85%

Multiple myeloma oncogene 1 (MUM1)/interferon regulatory factor 4 (IRF4) upregulates monokine induced by interferon-γ (MIG) gene expression in B-cell malignancy

et al. 2005

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MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) is a transcription factor that is activated as a result of t(6;14)(p25;q32) in multiple myeloma. MUM1 expression is seen in various B-cell lymphomas and predicts an unfavorable outcome in some lymphoma subtypes. To elucidate its role in B-cell malignancies, we prepared MUM1-expressing Ba/F3 cells, which proliferated until higher cellular density than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1. We found that the expression of four genes including FK506-binding protein 3 (FKBP3), the monokine induced by interferonc(MIG), Fas apoptotic inhibitory molecule (Faim) and Zinc-finger protein 94 was altered in the MUM1-expressing cells. We then focused on MIG since its expression was immediately upregulated by MUM1. In reporter assays, MUM1 activated the MIG promoter in cooperation with PU.1, and the interaction between MUM1 and the MIG promoter sequence was confirmed. The expression of MIG was correlated with that of MUM1 in B-CLL cell lines, and treatment with neutralizing antibodies against MIG and its receptor, CXCR3, slightly inhibited the proliferation of two MUM1-expressing lines. These results suggest that MUM1 plays roles in the progression of B-cell lymphoma/ leukemia by regulating the expression of various genes including MIG.

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“…Interferon-inducible T cell ␣ chemoattractant (I-TAC, or CXCL11) is another potent ligand for CXCR3 that is induced in a wide range of human tissues by IFN␥ (50). I-TAC is expressed together with IP-10 and Mig in some epithelial cells, such as gastric epithelial cells (51) and bronchial epithelial cells (52). It is possible that I-TAC, along with IP-10 and Mig, is also involved in the SS salivary gland lesions.…”

Section: Discussionmentioning

confidence: 99%

Involvement of the interferon‐γ–induced T cell–attracting chemokines, interferon‐γ–inducible 10‐kd protein (CXCL10) and monokine induced by interferon‐γ (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome

Ogawa

et al. 2002

Arthritis & Rheumatism

199

147

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Objective. To elucidate the mechanism of the development of T cell infiltrates in the salivary glands of patients with Sjögren's syndrome (SS), we studied T cell-attracting chemokines and their receptors.Methods. The expression of the T cell-attracting chemokines, interferon-␥ (IFN␥)-inducible 10-kd protein (IP-10; also called CXCL10), monokine induced by IFN␥ (Mig; also called CXCL9), and stromal cellderived factor 1 (SDF-1; also called CXCL12), in salivary glands from SS patients was investigated by polymerase chain reaction-enzyme-linked immunosorbent assay (ELISA). Cells that produce chemokines and lymphocytes that express chemokine receptors were identified by immunohistochemistry. The production of IP-10 and Mig proteins by salivary epithelial cells in response to IFN␥ was determined by ELISA.Results. Expression of IP-10 and Mig messenger RNA (mRNA) was significantly up-regulated in SS salivary glands compared with normal salivary glands (both P < 0.01). There was no significant difference in SDF-1 mRNA expression between the SS and normal salivary glands. IP-10 and Mig proteins were predominantly expressed in the ductal epithelium adjacent to lymphoid infiltrates. Most of the CD3؉ infiltrating lymphocytes in dense periductal foci expressed CXCR3, the receptor for IP-10 and Mig. IFN␥ induced the production of high levels of IP-10 and Mig proteins from cultured SS salivary epithelial cells.Conclusion. These findings suggest that IFN␥ stimulates the production of IP-10 and Mig in the SS ductal epithelium, and that IP-10 and Mig are involved in the accumulation of T cell infiltrates in the SS salivary gland. Chemokines or chemokine receptors could be a rational new therapeutic target in SS.

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IFN-γsynergizes with TNF-αbut not with viableH. pyloriin up-regulating CXC chemokine secretion in gastric epithelial cells

Cited by 38 publications

References 37 publications

Nucleotide Oligomerization Domain 1 Enhances IFN-γ Signaling in Gastric Epithelial Cells during Helicobacter pylori Infection and Exacerbates Disease Severity

Nucleotide Oligomerization Domain 1 Enhances IFN-γ Signaling in Gastric Epithelial Cells during Helicobacter pylori Infection and Exacerbates Disease Severity

Multiple myeloma oncogene 1 (MUM1)/interferon regulatory factor 4 (IRF4) upregulates monokine induced by interferon-γ (MIG) gene expression in B-cell malignancy

Involvement of the interferon‐γ–induced T cell–attracting chemokines, interferon‐γ–inducible 10‐kd protein (CXCL10) and monokine induced by interferon‐γ (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome

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