Studies On Endoplasmic Reticulum Stress Of Psoriatic Keratinocytes

Objective:Psoriasis is a common and chronic inflammatory skin disease, etiology and pathogenesis of psoriasis has not been completely illuminated. Lots of Studies have shown that endoplasmic reticulum stress (ERS) regulate inflammatory cytokines and contribute to the onset of inflammatory diseases. But the role of ERS in the pathogenesis of psoriasis has not been researched. So, we will take keratinocytes of psoriasis as research object to study the morphology of endoplasmic reticulum(ER), ERS marker Bip/GRP78 and Tumor Necrosis Factor alpha in keratinocytes of psoriasis. Our aim was to make clear the influence of endoplasmic reticulum stress to pathogenesis of psoriasis, explore the influence of endoplasmic reticulum stress to Tumor Necrosis Factor alpha secretion and provide a theoretical and experimental basis for understanding regulation of the inflammatory response of psoriasis.Methods:We asked for ethics committee approval of hospital. Vulgaris and acute psoriasis patients were research object, specimens of psoriatic lesion and healthy skin was got through surgery. The morphology of endoplasmic reticulum in keratinocytes was observed by TEM, to analyze the morphological changes of endoplasmic reticulum in keratinocytes of psoriasis; we used western blot and immunohistochemical method to check immunoglobulin heavy chain binding protein Bip/GRP78 and TNF-a in keratinocytes of specimens, to analysis the correlation of them.Result:(1) The structure and arrange of keratinocytes of control group was orderly, The small number of endoplasmic reticulum with normal morphology mainly concentrated around the nucleus. But keratinocytes of psoriasis was disorganized and metabolically active. Endoplasmic reticulum of psoriasis was inflated and dilated; (2) western blot results displayed:compared with control group, Bip/GRP78 and TNF-α were significantly higher with statistical signifLcance(P<0.001;.P< 0.01); (3) a small number of TNF-a and Bip/GRP78 distributed in the epidermis of the control group, mainly concentration distribution in the in epidermal basal cell layer. In the lesions of psoriasis, TNF-a and Bip/GRP78 was diffuse and distributed in the epidermis layer, with strong expression intensity compared with the control group. We also found TNF-a and Bip/GRP78 expressed around blood vessels in the dermis.(4) Bip/GRP78 and TNF-a were positively correlated in the lesions of psoriasis.Conclusions:Abnormal morphology of ER and strong expression of Bip/GRP78 in the lesions of psoriasis hint that endoplasmic reticulum stress may involved in the onset of psoriasis; Bip/GRP78 and TNF-a were positively correlated, a large amount of data shows that endoplasmic reticulum stress induce secretion of TNF-a. As a consequence, we speculate that endoplasmic reticulum stress in keratinocytes of psoriasis may regulate the production of TNF-a. We first put forward and proved endoplasmic reticulum stress plays an important role in the pathogenesis of psoriasis. Our study will provide theoretical and experimental basis for revealing the pathogenesis of psoriasis and reasonable treatment mechanism.