Abstract
Psoriasis is an inflammatory disease characterized by the abnormal proliferation of skin cells, including dermal microvascular endothelial cells. Recently, chemokine-like factor 1 (CKLF1) was found to participate in the local inflammation and cell proliferation. To explore its role in the pathogenesis of psoriasis, the expression of both CKLF1 and its receptor (CCR4) was determined in the psoriatic lesions. Also, the effect of the C-terminal peptides (C19 and C27) of CKLF1 on the proliferation of human umbilical vein endothelial cells was studied in vitro. By immunohistochemistry and immunofluorescence, the expression of both CKLF1 and CCR4 was determined in the psoriatic lesions. The effect of C-terminal peptides on human umbilical vein endothelial cells (HUVECs) was studied in vitro by the evaluation of cell proliferation and apoptosis. The in vivo assessment was performed accordingly through the subcutaneous injection peptides on BALB/c mice. The results showed that, by immunohistochemistry, both CKLF1 and CCR4 were increasingly expressed in psoriatic lesions as compared to normal skins. Moreover, the primary umbilical vein endothelial cells exhibited higher proliferation ratio under the C19 or C27 stimulation, which was even enhanced by the addition of psoriatic sera or TNF-α. Furthermore, the enhancement of peptide simulation was accompanied with the activation of ERK1/2-MAPKs pathway. In addition, such effect of C19 and C27 was mirrored by the hyperproliferation of cutaneous microvessels in BALB/c mice that were subcutaneously injected with the two peptides. Therefore, we concluded that CKLF1 plays a role in the pathogenesis of psoriasis by promoting the proliferation of microvascular endothelial cells that possibly correlates with ERK1/2-MAPKs activation.
Highlights
Psoriasis is an inflammatory skin disorder characterized by the epidermis hyperproliferation, inflammatory cell accumulation, and dilation of dermal papillary blood vessels [1]
The results showed that both chemokine-like factor 1 (CKLF1) and chemokine receptor 4 (CCR4) were highly expressed in the skin lesion from the patients with psoriasis
Primary human umbilical vein endothelial cells (HUVECs) synthesized more CCR4 and CKLF1 as either psoriatic sera or tumor necrosis factor (TNF)-α was added to culture media
Summary
Psoriasis is an inflammatory skin disorder characterized by the epidermis hyperproliferation, inflammatory cell accumulation, and dilation of dermal papillary blood vessels [1]. More supportive evidences have shown that certain chemokines and their receptors are involved in the progression of psoriatic lesion, possibly by participating in the process of leukocyte recruitment and activation at the sites of local inflammation [4,5,6,7]. These molecules regulate endothelial cell functions, such as proliferation, migration, angiogenesis, and adhesion molecule expression, all of which contribute to the manifestations of psoriasis [8,9,10]. To investigate the function of these cytokines in regulating microvascular endothelial cells is helpful for the elucidation of pathogenesis and the exploration of novel therapeutic targets
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