Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 3706-3715 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 190 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2013 |
Cite this
}
Nucleotide oligomerization domain 1 enhances IFN-gamma signaling in gastric epithelial cells during Helicobacter pylori infection and exacerbates disease severity. / Allison, Cody Charles; Ferrand, Jonathan Francois Patrice; McLeod, Louise; Hassan, Mohammad; Kaparakis-Liaskos, Maria; Grubman, Alexandra; Bhathal, Prithi S; Dev, Anouk Tara; Sievert, William; Jenkins, Brendan John; Ferrero, Richard Louis.
In: Journal of Immunology, Vol. 190, No. 7, 2013, p. 3706-3715.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Nucleotide oligomerization domain 1 enhances IFN-gamma signaling in gastric epithelial cells during Helicobacter pylori infection and exacerbates disease severity
AU - Allison, Cody Charles
AU - Ferrand, Jonathan Francois Patrice
AU - McLeod, Louise
AU - Hassan, Mohammad
AU - Kaparakis-Liaskos, Maria
AU - Grubman, Alexandra
AU - Bhathal, Prithi S
AU - Dev, Anouk Tara
AU - Sievert, William
AU - Jenkins, Brendan John
AU - Ferrero, Richard Louis
PY - 2013
Y1 - 2013
N2 - 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-gamma-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-gamma stimulation through the direct effects of H. pylori on two components of the IFN-gamma 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-Tyr(701)/Ser(727) phosphorylation and IRF1 expression/synthesis in cells, resulting in enhanced production of the NOD1- and IFN-gamma-regulated chemokines, IL-8- and IFN-gamma-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-gamma signaling pathways contribute to H. pylori-induced inflammatory responses, potentially revealing a novel mechanism whereby virulent H. pylori strains promote more severe disease.
AB - 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-gamma-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-gamma stimulation through the direct effects of H. pylori on two components of the IFN-gamma 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-Tyr(701)/Ser(727) phosphorylation and IRF1 expression/synthesis in cells, resulting in enhanced production of the NOD1- and IFN-gamma-regulated chemokines, IL-8- and IFN-gamma-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-gamma signaling pathways contribute to H. pylori-induced inflammatory responses, potentially revealing a novel mechanism whereby virulent H. pylori strains promote more severe disease.
UR - http://www.ncbi.nlm.nih.gov/pubmed/23460743
U2 - 10.4049/jimmunol.1200591
DO - 10.4049/jimmunol.1200591
M3 - Article
VL - 190
SP - 3706
EP - 3715
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -