title: Up-regulation of CC chemokine ligand 20 and its receptor CCR6 in the lesional skin of early systemic sclerosis.
abstract: Mononuclear cell (MNC) infiltrate is one of the earliest pathological changes in systemic sclerosis (SSc) skin. However, little is known about the recruitment of these cells into skin lesions. Recently, the role of chemokines has been suggested in the pathogenesis of SSc. Here we studied the expressions and distributions of CC chemokine CCL20 and its receptor CCR6 in early SSc skin lesions and the difference in CCL20 expressions and ability to recruite MNCs of normal dermal fibroblast (NDF) and scleroderma dermal fibroblast (SSDF). We found that the expressions of CCL20 and its receptor CCR6 were obviously up-regulated in SSc in contrast to normal human skin. mRNA levels were significantly expressed in SSc lesional skins vs normal skin tissues. SSDF displayed increased constitutive expressions of CCL20 mRNA and protein. In addition, Th1 cytokines (TNF-α and IL-1β) remarkably increased the expression of CCL20 in both NDF and SSDF in a dose- and time-dependent manner. Supernatants from SSDF showed stronger chemotactic activity to PBMCs than those from NDF. Thus our findings suggest that CCL20 released from cytokine-activated SSDF plays an important role in the induction of SSc by further recruiting more MNCs to the skin.
authors: Department of Dermatology, Huazhong University of Science and Technology, Wuhan, China.
authors: Juan
authors: J
authors: Tao
authors: Lin
authors: L
authors: Li
authors: Zhijian
authors: Z
authors: Tan
authors: Yan
authors: Y
authors: Li
authors: Jing
authors: J
authors: Yang
authors: Fen
authors: F
authors: Tian
authors: Li
authors: L
authors: Wang
authors: Yali
authors: Y
authors: Ren
authors: Guangfen
authors: G
authors: Xu
authors: Xiaoliang
authors: X
authors: He
authors: Guanxin
authors: G
authors: Shen
authors: Yating
authors: Y
authors: Tu
mesh_terms: D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008297:Male; D054399:Receptors, CCR6 / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C106311:CCR6 protein, human; D054418:Chemokine CCL20; D007378:Interleukins; D054399:Receptors, CCR6; D014409:Tumor Necrosis Factor-alpha