| First Author | De Dios R | Year | 2020 |
| Journal | Immunology | Volume | 160 |
| Issue | 1 | Pages | 64-77 |
| PubMed ID | 32064589 | Mgi Jnum | J:298120 |
| Mgi Id | MGI:6471233 | Doi | 10.1111/imm.13182 |
| Citation | De Dios R, et al. (2020) CpG-ODN-mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFkappaB inhibitory protein IkappaBbeta to drive IL1alpha and IL1beta expression. Immunology 160(1):64-77 |
| abstractText | Sterile inflammation contributes to many pathological states associated with mitochondrial injury. Mitochondrial injury disrupts calcium homeostasis and results in the release of CpG-rich mitochondrial DNA. The role of CpG-stimulated TLR9 innate immune signalling and sterile inflammation is well studied; however, how calcium dyshomeostasis affects this signalling is unknown. Therefore, we interrogated the relationship betauween intracellular calcium and CpG-induced TLR9 signalling in murine macrophages. We found that CpG-ODN-induced NFkappaB-dependent IL1alpha and IL1beta expression was significantly attenuated by both calcium chelation and calcineurin inhibition, a finding mediated by inhibition of degradation of the NFkappaB inhibitory protein IkappaBbeta. In contrast, calcium ionophore exposure increased CpG-induced IkappaBbeta degradation and IL1alpha and IL1beta expression. These results demonstrate that through its effect on IkappaBbeta degradation, increased intracellular Ca(2+) drives a pro-inflammatory TLR9-mediated innate immune response. These results have implications for the study of innate immune signalling downstream of mitochondrial stress and injury. |
