Unknown

Dataset Information

0

TLR2 Activation Limits Rhinovirus-Stimulated CXCL-10 by Attenuating IRAK-1-Dependent IL-33 Receptor Signaling in Human Bronchial Epithelial Cells.


ABSTRACT: Airway epithelial cells are the major target for rhinovirus (RV) infection and express proinflammatory chemokines and antiviral cytokines that play a role in innate immunity. Previously, we demonstrated that RV interaction with TLR2 causes ILR-associated kinase-1 (IRAK-1) depletion in both airway epithelial cells and macrophages. Further, IRAK-1 degradation caused by TLR2 activation was shown to inhibit ssRNA-induced IFN expression in dendritic cells. Therefore, in this study, we examined the role of TLR2 and IRAK-1 in RV-induced IFN-?, IFN-?1, and CXCL-10, which require signaling by viral RNA. In airway epithelial cells, blocking TLR2 enhanced RV-induced expression of IFNs and CXCL-10. By contrast, IRAK-1 inhibition abrogated RV-induced expression of CXCL-10, but not IFNs in these cells. Neutralization of IL-33 or its receptor, ST2, which requires IRAK-1 for signaling, inhibited RV-stimulated CXCL-10 expression. In addition, RV induced expression of both ST2 and IL-33 in airway epithelial cells. In macrophages, however, RV-stimulated CXCL-10 expression was primarily dependent on TLR2/IL-1R. Interestingly, in a mouse model of RV infection, blocking ST2 not only attenuated RV-induced CXCL-10, but also lung inflammation. Finally, influenza- and respiratory syncytial virus-induced CXCL-10 was also found to be partially dependent on IL-33/ST2/IRAK-1 signaling in airway epithelial cells. Together, our results indicate that RV stimulates CXCL-10 expression via the IL-33/ST2 signaling axis, and that TLR2 signaling limits RV-induced CXCL-10 via IRAK-1 depletion at least in airway epithelial cells. To our knowledge, this is the first report to demonstrate the role of respiratory virus-induced IL-33 in the induction of CXCL-10 in airway epithelial cells.

SUBMITTER: Ganesan S 

PROVIDER: S-EPMC5070654 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

TLR2 Activation Limits Rhinovirus-Stimulated CXCL-10 by Attenuating IRAK-1-Dependent IL-33 Receptor Signaling in Human Bronchial Epithelial Cells.

Ganesan Shyamala S   Pham Duc D   Jing Yaxun Y   Farazuddin Mohammad M   Hudy Magdalena H MH   Unger Benjamin B   Comstock Adam T AT   Proud David D   Lauring Adam S AS   Sajjan Uma S US  

Journal of immunology (Baltimore, Md. : 1950) 20160808 6


Airway epithelial cells are the major target for rhinovirus (RV) infection and express proinflammatory chemokines and antiviral cytokines that play a role in innate immunity. Previously, we demonstrated that RV interaction with TLR2 causes ILR-associated kinase-1 (IRAK-1) depletion in both airway epithelial cells and macrophages. Further, IRAK-1 degradation caused by TLR2 activation was shown to inhibit ssRNA-induced IFN expression in dendritic cells. Therefore, in this study, we examined the ro  ...[more]

Similar Datasets

| S-EPMC3464227 | biostudies-other
| S-EPMC7533303 | biostudies-literature
2008-03-08 | GSE10765 | GEO
| S-EPMC6689742 | biostudies-literature
| S-EPMC5913134 | biostudies-literature
| S-EPMC7124215 | biostudies-literature
| S-EPMC3976391 | biostudies-literature
2008-04-05 | E-GEOD-10765 | biostudies-arrayexpress
| S-EPMC2383991 | biostudies-literature
| S-EPMC4550463 | biostudies-literature