| First Author | Akita K | Year | 2017 |
| Journal | Front Cardiovasc Med | Volume | 4 |
| Pages | 84 | PubMed ID | 29312959 |
| Mgi Jnum | J:288944 | Mgi Id | MGI:6433544 |
| Doi | 10.3389/fcvm.2017.00084 | Citation | Akita K, et al. (2017) An Interleukin-6 Receptor Antibody Suppresses Atherosclerosis in Atherogenic Mice. Front Cardiovasc Med 4:84 |
| abstractText | IkappaBNS is a nuclear IkappaB protein which negatively regulates nuclear factor-kappaB activity. We demonstrated that IkappaBNS deficiency accelerates atherosclerosis in LDL receptor-deficient (LDLr(-/-)) mice via increased interleukin (IL)-6 production by macrophages. Previous studies showed that the increase in IL-6 might contribute to the development of atherosclerotic lesions. However, whether an anti-mouse IL-6 receptor antibody (MR16-1) can protect atherosclerotic lesions in atherogenic mice remains to be elucidated. We investigated atherosclerotic lesions in LDLr(-/-) and IkappaBNS(-/-)/LDLr(-/-) mice after 16 weeks consumption of a high-fat diet. All mice received intraperitoneal injections of MR16-1 or phosphate-buffered saline (PBS) (control) once a week during a high-fat diet consumption. Treatment of MR16-1 yielded no adverse systemic effects, and we detected no significant differences in serum cholesterol levels in either group. The atherosclerotic lesions were significantly increased in IkappaBNS(-/-)/LDLr(-/-) compared with LDLr(-/-) mice (p < 0.01) under treatment of PBS. However, MR16-1 treatment abolished the significant difference of atherosclerotic lesions between IkappaBNS(-/-)/LDLr(-/-) and LDLr(-/-) mice. Interestingly, MR16-1 also significantly decreased atherosclerotic lesions in LDLr(-/-) mice compared with PBS treatment (p < 0.05). Immunostaining revealed percent phospho-STAT3-positive cell were significantly decreased in the atherosclerotic lesions of MR16-1 treated both IkappaBNS(-/-)/LDLr(-/-) and LDLr(-/-) mice compared with PBS-treated mice, indicating MR16-1 could suppress atherosclerotic lesions via the inhibition of IL-6-STAT3 signaling pathway. This study highlights the potential therapeutic benefit of anti-IL-6 therapy in preventing atherogenesis induced by dyslipidemia and/or inflammation. |
