中山醫學大學機構典藏 CSMUIR:Item 310902500/23739
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    题名: Cultured Human Uveal Melanocytes Express/secrete CXCL1 and CXCL2 Constitutively and Increased by Lipopolysaccharide via Activation of Toll-like Receptor 4
    作者: Hu, DN;Zhang, RH;Yao, S;Iacob, CE;Yang, WE;Rosen, R;Yang, SF
    关键词: Uveal melanocytes;CXCL1;CXCL2;lipopolysaccharide;Toll-like receptor 4
    日期: 2021
    上传时间: 2022-08-05T09:42:05Z (UTC)
    出版者: TAYLOR & FRANCIS INC
    ISSN: 0271-3683
    摘要: Purpose: Lipopolysaccharide (LPS) can activate Toll-like receptor 4 (TLR4) and increase the expression of CXCL1 and CXCL2, the potent neutrophils chemoattractants, in various cell types. These effects have not been previously reported in the uveal melanocytes. This study was designed to investigate the effects of LPS on the activation of TLR4 and expression of CXCL1/CXCL2 in cultured human uveal melanocytes and the relevant signal pathways. Methods: Effects of LPS on the expression of TLR4 were tested using real-time PCR, flow cytometry and fluorescence immunostaining. Effects of LPS-induced expression/secretion of CXCL1/CXCL2 were studied using real-time PCR in cell lysates and ELISA in conditioned media of cultured uveal melanocytes. Activated NF-kappa B and phosphorylated MAPK signals were tested in cells with and without LPS treatment using flow cytometry. Effects of various signal inhibitors on p38, ERK1/2, JNK1/2 and NF-kappa B on the secretion of CXCL1/CXCL2 were tested by ELISA. The effects of neutralized antibodies of CXCL1/CXCL2 on the severity of LPS-induced uveitis were tested in a mouse model. Results: LPS stimulation increased the expression of TLR4 mRNA and protein in culture uveal melanocytes. Constitutive secretion of CXCL1/CXCL2 was detected in uveal melanocytes and was significantly increased dose- and time-dependently by LPS stimulation. LPS mainly increased the activated NF-kappa B and phosphorylated JNK1/2. LPS-induced expression of CXCL1/CXCL2 was blocked by NF-kappa B and JNK1/2 inhibitors. The severity of LPS-induced uveitis was significantly inhibited by neutralizing antibody to CXCL1/CXCL2 Conclusions: This is the first report on the LPS-induced expression of CXCL1 and CXCL2 by uveal melanocytes via the activation of TLR4. These results suggest that uveal melanocytes may play a role in the immune reaction that eliminates the invading pathogens. Conversely, an excessive LPS-induced inflammatory reaction may also lead to the development of inflammatory ocular disorders, such as non-infectious uveitis.
    URI: http://dx.doi.org/10.1080/02713683.2021.1929326
    https://www.webofscience.com/wos/woscc/full-record/WOS:000655395600001
    https://ir.csmu.edu.tw:8080/handle/310902500/23739
    關聯: CURRENT EYE RESEARCH ,2021,v46,issue 11, P1681-1694
    显示于类别:[中山醫學大學研究成果] 期刊論文

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