The nuclear factor ?B (NF-?B) pathway plays a key role in innate and adaptive immunity, cell proliferation and survival, inflammation and tumors development. MiR-146a is an immune system regulator that has anti-inflammatory function in multiple cell types and conditions. Here we demonstrate activation of canonical NF-?B pathway in monocytic cells upon HSV-1 replication. By constructing and using a recombinant HSV-1\EGFP virus, we monitored the capability of the virus to recruit NF-?B and we report that the phosphorylation of p65 protein correlates with an active virus replication at single-cell level. In addition, we found that upregulation of miR-146a during viral replication is strictly dependent on NF-?B activation and correlates with tight control of the interleukin-1 receptor-associate kinase 1 (IRAK1). Accordingly, THP-1 DN I?B? cells, expressing a dominant negative mI?B?, did not show upregulation of miR-146a upon HSV-1 infection. Our data suggest that the expression of miRNA-146a modulates NF-?B activation through targeting IRAK1 during HSV-1 replication in THP-1 cells.
HSV-1\EGFP stimulates miR-146a expression in a NF-?B-dependent manner in monocytic THP-1 cells
Mastino A;
2019
Abstract
The nuclear factor ?B (NF-?B) pathway plays a key role in innate and adaptive immunity, cell proliferation and survival, inflammation and tumors development. MiR-146a is an immune system regulator that has anti-inflammatory function in multiple cell types and conditions. Here we demonstrate activation of canonical NF-?B pathway in monocytic cells upon HSV-1 replication. By constructing and using a recombinant HSV-1\EGFP virus, we monitored the capability of the virus to recruit NF-?B and we report that the phosphorylation of p65 protein correlates with an active virus replication at single-cell level. In addition, we found that upregulation of miR-146a during viral replication is strictly dependent on NF-?B activation and correlates with tight control of the interleukin-1 receptor-associate kinase 1 (IRAK1). Accordingly, THP-1 DN I?B? cells, expressing a dominant negative mI?B?, did not show upregulation of miR-146a upon HSV-1 infection. Our data suggest that the expression of miRNA-146a modulates NF-?B activation through targeting IRAK1 during HSV-1 replication in THP-1 cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
