| First Author | Mejías-Luque R | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 7030 |
| PubMed ID | 31065023 | Mgi Jnum | J:279840 |
| Mgi Id | MGI:6357453 | Doi | 10.1038/s41598-019-43417-x |
| Citation | Mejias-Luque R, et al. (2019) Increased LIGHT expression and activation of non-canonical NF-kappaB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection. Sci Rep 9(1):7030 |
| abstractText | Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis. Among those, NF-kappaB signaling plays a pivotal role during infection and malignant transformation of the gastric epithelium. However, deficiency of the adaptor molecule myeloid differentiation primary response 88 (MyD88), which signals through NF-kappaB, led to an accelerated development of gastric pathology upon H. felis infection, but the mechanisms leading to this phenotype remained elusive. Non-canonical NF-kappaB signaling was shown to aggravate H. pylori-induced gastric inflammation via activation of the lymphotoxin beta receptor (LTbetaR). In the present study, we explored whether the exacerbated pathology observed in MyD88-deficient (Myd88(-/-)) mice was associated with aberrant activation of non-canonical NF-kappaB. Our results indicate that, in the absence of MyD88, H. felis infection enhances the activation of non-canonical NF-kappaB that is associated with increase in Cxcl9 and Icam1 gene expression and CD3(+) lymphocyte recruitment. In addition, activation of signal transducer and activator of transcription 3 (STAT3) signaling was higher in Myd88(-/-) compared to wild type (WT) mice, indicating a link between MyD88 deficiency and STAT3 activation in response to H. felis infection. Thereby, MyD88 deficiency results in accelerated and aggravated gastric pathology induced by Helicobacter through activation of non-canonical NF-kappaB. |
