Mechanisms
CETP-overexpressing mice develop worse psoriasis-like skin lesions with higher inflammatory cytokines than normal mice (Lipids Health Dis 2022)
Original title: Elevated cholesteryl ester transfer and phospholipid transfer proteins aggravated psoriasis in imiquimod-induced mouse models
Psoriasis is a chronic inflammatory skin disease linked to dyslipidaemia and reduced HDL, and this study tested whether elevated CETP or phospholipid transfer protein (PLTP), both known to lower HDL when overexpressed, worsen disease in an imiquimod-induced psoriasis mouse model. CETP-transgenic and PLTP-transgenic mice developed higher clinical and histological psoriasis severity scores than wild-type mice, with more proliferating skin cells in psoriatic lesions. mRNA levels of interferon-alpha, IL-1beta, IL-6, IL-17A, IL-17F, IL-22 and IL-23p19 all rose more in CETP-transgenic and PLTP-transgenic mice than in wild-type mice, and plasma TNF-alpha, though not IL-6, was also higher. The authors conclude elevated CETP and PLTP aggravate psoriasis in this mouse model, a novel non-cardiovascular indication where CETP overexpression itself, rather than a CETP inhibitor drug, is the exposure studied.
Original abstract
Background: Psoriasis is a chronic inflammatory skin disorder related to dyslipidemia, with decreased high-density lipoprotein (HDL). Various cell types express phospholipid transfer protein (PLTP) as well as cholesteryl ester transfer protein (CETP). Their elevated levels among transgenic (Tg) mice led to reduced HDL and a higher risk of atherosclerosis (AS). This study examined whether elevated CETP and PLTP could aggravate psoriasis in a psoriasis vulgaris mouse model.
Methods: The back skins of CETP-Tg, PLTP-Tg, and C57BL/6 male mice, aged six to 8 weeks, were shaved for imiquimod cream (IMQ) (5%) treatment for five consecutive days. The clinical pathological parameters were rated independently using the modified target lesion psoriasis severity score. The skin sections stained with hematoxylin-eosin were scored by the Baker score. Epidermal thickening and differentiation and inflammatory factor infiltration were determined by immunohistochemistry. Inflammatory cytokine levels were measured using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. This work employed SPSS Statistics Version to conduct statistical analyses.
Results: In this study, CETP-Tg and PLTP-Tg mice had higher clinical and histological scores than wild-type (WT) mice. Immunohistochemistry of the epidermis and dermis revealed a high proportion of proliferating cell nuclear antigen (PCNA) positivity within psoriatic skin lesions of CETP-Tg and PLTP-Tg mice compared with WT mice. Interferon-α (IFN-α), interleukin-1β (IL-1β), IL-6, IL-17A, IL-17F, IL-22, and IL-23p19 mRNA levels increased within CETP-Tg and PLTP-Tg mice compared with WT counterparts. In comparison with WT mice, plasma tumor necrosis factor-α (TNF-α) levels, rather than IL-6 levels, were increased in CETP-Tg and PLTP-Tg mice.
Conclusions: Elevated CETP and PLTP aggravate psoriasis in a imiquimod-induced mouse model.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.