Yan Shu1, Da-Zhi Yang1, Jia Liang1, Feng Zhang1, Bing Wang1, Hong-Bing Yao1, En-Mei Liu2. 1. Department of Otolaryngology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Infection and Immunity Chongqing 400014, China. 2. Department of Respiration Medicine, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Infection and Immunity Chongqing 400014, China.
Abstract
PURPOSE: This study aims to determine whether leukotriene D4 (LTD4) can promote T cell proliferation in adenoid tissues via activation of CysLT1 receptors in children with OSAS. METHODS: CD4+ and CD8+ T cell proliferation was assessed by flow cytometry in adenoid mononuclear cells (AdMCs) stimulated with LTD4 from children with OSAS. The activation of mitogen-activated protein kinase pathways and their effects on the proliferation of CD4+ and CD8+ T cells in AdMCs were observed by western blotting. RESULTS: LTD4 increased the proliferation rates of both phytohemagglutinin (PHA)-stimulated CD4+ T cells (15.5±8.4% in the PHA group vs. 24.8±6.3% in the PHA+LTD4 group; n=27; P<0.001) and CD8+ T cells (17.2±5.9% in the PHA group vs. 23.5±5.2% in the PHA+LTD4 group; n=27; P<0.05) in AdMCs. LTD4 (10-4 mmol) significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, but not c-Jun N-terminal kinases (JNK). The ERK1/2 inhibitor PD98059 significantly inhibited the proliferation of CD4+ and CD8+ T cells in LTD4-stimulated AdMCs. CONCLUSION: LTD4 regulates the proliferation of CD4+ and CD8+ T cells in PHA-stimulated AdMCs via upregulation of the ERK1/2 pathway. This finding indicates that CysLT1 receptors play a regulatory role in the pathogenesis of OSAS in children.
PURPOSE: This study aims to determine whether leukotriene D4 (LTD4) can promote T cell proliferation in adenoid tissues via activation of CysLT1 receptors in children with OSAS. METHODS: CD4+ and CD8+ T cell proliferation was assessed by flow cytometry in adenoid mononuclear cells (AdMCs) stimulated with LTD4 from children with OSAS. The activation of mitogen-activated protein kinase pathways and their effects on the proliferation of CD4+ and CD8+ T cells in AdMCs were observed by western blotting. RESULTS: LTD4 increased the proliferation rates of both phytohemagglutinin (PHA)-stimulated CD4+ T cells (15.5±8.4% in the PHA group vs. 24.8±6.3% in the PHA+LTD4 group; n=27; P<0.001) and CD8+ T cells (17.2±5.9% in the PHA group vs. 23.5±5.2% in the PHA+LTD4 group; n=27; P<0.05) in AdMCs. LTD4 (10-4 mmol) significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, but not c-Jun N-terminal kinases (JNK). The ERK1/2 inhibitor PD98059 significantly inhibited the proliferation of CD4+ and CD8+ T cells in LTD4-stimulated AdMCs. CONCLUSION: LTD4 regulates the proliferation of CD4+ and CD8+ T cells in PHA-stimulated AdMCs via upregulation of the ERK1/2 pathway. This finding indicates that CysLT1 receptors play a regulatory role in the pathogenesis of OSAS in children.
Authors: Albert M Li; Hung K So; Chun T Au; Crover Ho; Joseph Lau; Siu K Ng; Victor J Abdullah; Tai F Fok; Yun K Wing Journal: Thorax Date: 2010-11 Impact factor: 9.139
Authors: Dinender Kumar; Vijayan Menon; William R Ford; Alexander S Clanachan; Bodh I Jugdutt Journal: J Cardiovasc Pharmacol Ther Date: 2003-12 Impact factor: 2.457