| First Author | Shaheen ZR | Year | 2019 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 316 |
| Issue | 5 | Pages | R525-R534 |
| PubMed ID | 30811246 | Mgi Jnum | J:277806 |
| Mgi Id | MGI:6295635 | Doi | 10.1152/ajpregu.00019.2019 |
| Citation | Shaheen ZR, et al. (2019) CCR5 is a required signaling receptor for macrophage expression of inflammatory genes in response to viral double-stranded RNA. Am J Physiol Regul Integr Comp Physiol 316(5):R525-R534 |
| abstractText | Double-stranded (ds) RNA, both synthetic and produced during virus replication, rapidly stimulates MAPK and NF-kappaB signaling that results in expression of the inflammatory genes inducible nitric oxide synthase, cyclooxygenase 2, and IL-1beta by macrophages. Using biochemical and genetic approaches, we have identified the chemokine ligand-binding C-C chemokine receptor type 5 (CCR5) as a cell surface signaling receptor required for macrophage expression of inflammatory genes in response to dsRNA. Activation of macrophages by synthetic dsRNA does not require known dsRNA receptors, as poly(inosinic:cytidylic) acid [poly(I:C)] activates signaling pathways leading to expression of inflammatory genes to similar levels in wild-type and Toll-like receptor 3- or melanoma differentiation antigen 5-deficient macrophages. In contrast, macrophage activation in response to poly(I:C) is attenuated in macrophages isolated from mice lacking CCR5. These findings support a role for CCR5 as a cell surface signaling receptor that participates in activation of inflammatory genes in macrophages in response to the viral dsRNA mimetic poly(inosinic:cytidylic) acid by pathways that are distinct from classical dsRNA receptor-mediated responses. |
