TY - JOUR
T1 - Imiquimod-Induced Psoriasis-Like Skin Lesions Do Not Accelerate Atherosclerosis in Low-Density Lipoprotein ReceptorDeficient Mice
AU - Madsen, Marie
AU - Hansen, Peter R.
AU - Nielsen, Lars B.
AU - Cardoso, Renata M.
AU - van Eck, Miranda
AU - Pedersen, Tanja X.
PY - 2018/6
Y1 - 2018/6
N2 - 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 receptorrelated orphan nuclear receptor gamma t, and attenuates IL-17dependent pathologies in mice. We investigated whether cyclic imiquimod-induced psoriasis-like skin inflammation affects atherosclerosis in low-density lipoprotein receptordeficient 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 receptordeficient 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 lipoproteindeficient mice. In this model, digoxin reduces skin inflammation, but it has no effect on atherosclerosis.
AB - 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 receptorrelated orphan nuclear receptor gamma t, and attenuates IL-17dependent pathologies in mice. We investigated whether cyclic imiquimod-induced psoriasis-like skin inflammation affects atherosclerosis in low-density lipoprotein receptordeficient 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 receptordeficient 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 lipoproteindeficient mice. In this model, digoxin reduces skin inflammation, but it has no effect on atherosclerosis.
U2 - 10.1016/j.ajpath.2018.02.005
DO - 10.1016/j.ajpath.2018.02.005
M3 - Journal article
C2 - 29545199
SN - 0002-9440
VL - 188
SP - 1486
EP - 1496
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -