| First Author | Madsen M | Year | 2018 |
| Journal | Am J Pathol | Volume | 188 |
| Issue | 6 | Pages | 1486-1496 |
| PubMed ID | 29545199 | Mgi Jnum | J:263893 |
| Mgi Id | MGI:6192880 | Doi | 10.1016/j.ajpath.2018.02.005 |
| Citation | Madsen M, et al. (2018) Imiquimod-Induced Psoriasis-Like Skin Lesions Do Not Accelerate Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice. Am J Pathol 188(6):1486-1496 |
| abstractText | Psoriasis is a chronic inflammatory skin disorder associated with several comorbidities, including atherosclerosis. Disease mechanisms that may affect both psoriasis and atherosclerosis include activation of T helper 1 and T helper 17 cells. Imiquimod application is an established mouse model of psoriasis-like skin inflammation. The cardiac glycoside digoxin inhibits the master transcription factor of T helper 17 differentiation, retinoid acid receptor-related orphan nuclear receptor gammat, and attenuates IL-17-dependent pathologies in mice. We investigated whether cyclic imiquimod-induced psoriasis-like skin inflammation affects atherosclerosis in low-density lipoprotein receptor-deficient mice and whether digoxin modifies either disease. Topical imiquimod application increased ear thickness, keratinocyte proliferation, and accumulation of CD3(+) T cells in the skin of low-density lipoprotein receptor-deficient mice. Also, imiquimod affected the mice systemically with induction of splenomegaly as well as increased plasma levels of IL-17A and serum amyloid A. Overall, imiquimod reduced atherosclerosis in the aortic arch en face, but it did not affect atherosclerosis in the aortic root. Digoxin significantly reduced the imiquimod-induced ear thickening, had divergent effects on imiquimod-induced systemic inflammation, and did not affect atherosclerosis. In conclusion, cyclic imiquimod applications can be used for long-term induction of psoriasis-like skin lesions, but they attenuate atherosclerosis in low-density lipoprotein-deficient mice. In this model, digoxin reduces skin inflammation, but it has no effect on atherosclerosis. |
