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The inhibition of TNF-alpha-induced E-selectin expression in endothelial cells via the JNK/NF-kappaB pathways by highly N-acetylated chitooligosaccharides.
Biomaterials. 2007 Mar; 28(7):1355-66.B

Abstract

Chitooligosaccharides (COS) have been shown to regulate various cellular and biological functions. However, the effect of COS on inflammatory responses of the cells remains unclear. We investigated the regulatory effect of highly N-acetylated COS (NACOS) on tumor necrosis factor-alpha (TNF-alpha)-induced endothelial cell (EC) E-selectin expression, which is crucial for leukocyte recruitment. ECs were kept as controls or pre-treated with NACOS for different times, and then stimulated with TNF-alpha for 4h. The results show that pre-treating ECs with NACOS inhibited the TNF-alpha-induced E-selectin expression in a dose- and time-dependent manner. This NACOS-mediated inhibition in E-selectin expression was regulated at the transcriptional level, but not due to changes in mRNA stability. Stimulation of ECs with TNF-alpha-induced rapid increases in the phosphorylation of their mitogen-activated protein kinases (MAPKs) [extracellular signal-regulated kinase (ERK), c-Jun-NH2-terminal kinase (JNK), and p38 MAPK]; the inhibitor for JNK (i.e., SP600125), but not those for ERK (i.e., PD98059) and p38 MAPK (i.e., SB203580), attenuated this TNF-alpha-induced E-selectin expression. Pre-treating ECs with NACOS inhibited the TNF-alpha-induced JNK activation, suggesting that JNK was involved in the inhibitory effect of NACOS on TNF-alpha-induced E-selectin expression. Pre-treating ECs with NACOS inhibited the TNF-alpha-induced p65 and p50 mRNA expressions. Gel shifting and chromatin immunoprecipitation assays showed that NACOS blocked the TNF-alpha-induced increases in the binding activity and in vivo promoter binding of nuclear factor-kappaB (NF-kappaB) in ECs. Our findings provide a molecular mechanism by which NACOS inhibit TNF-alpha-induced E-selectin expression in ECs, and a basis for using NACOS in pharmaceutical therapy against inflammation.

Authors+Show Affiliations

Division of Medical Engineering Research, National Health Research Institutes, Miaoli 350, Taiwan, ROC.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17126899

Citation

Lin, Chia-Wen, et al. "The Inhibition of TNF-alpha-induced E-selectin Expression in Endothelial Cells Via the JNK/NF-kappaB Pathways By Highly N-acetylated Chitooligosaccharides." Biomaterials, vol. 28, no. 7, 2007, pp. 1355-66.
Lin CW, Chen LJ, Lee PL, et al. The inhibition of TNF-alpha-induced E-selectin expression in endothelial cells via the JNK/NF-kappaB pathways by highly N-acetylated chitooligosaccharides. Biomaterials. 2007;28(7):1355-66.
Lin, C. W., Chen, L. J., Lee, P. L., Lee, C. I., Lin, J. C., & Chiu, J. J. (2007). The inhibition of TNF-alpha-induced E-selectin expression in endothelial cells via the JNK/NF-kappaB pathways by highly N-acetylated chitooligosaccharides. Biomaterials, 28(7), 1355-66.
Lin CW, et al. The Inhibition of TNF-alpha-induced E-selectin Expression in Endothelial Cells Via the JNK/NF-kappaB Pathways By Highly N-acetylated Chitooligosaccharides. Biomaterials. 2007;28(7):1355-66. PubMed PMID: 17126899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The inhibition of TNF-alpha-induced E-selectin expression in endothelial cells via the JNK/NF-kappaB pathways by highly N-acetylated chitooligosaccharides. AU - Lin,Chia-Wen, AU - Chen,Li-Jing, AU - Lee,Pei-Ling, AU - Lee,Chih-I, AU - Lin,Jui-Che, AU - Chiu,Jeng-Jiann, Y1 - 2006/11/28/ PY - 2006/09/05/received PY - 2006/11/03/accepted PY - 2006/11/28/pubmed PY - 2007/3/8/medline PY - 2006/11/28/entrez SP - 1355 EP - 66 JF - Biomaterials JO - Biomaterials VL - 28 IS - 7 N2 - Chitooligosaccharides (COS) have been shown to regulate various cellular and biological functions. However, the effect of COS on inflammatory responses of the cells remains unclear. We investigated the regulatory effect of highly N-acetylated COS (NACOS) on tumor necrosis factor-alpha (TNF-alpha)-induced endothelial cell (EC) E-selectin expression, which is crucial for leukocyte recruitment. ECs were kept as controls or pre-treated with NACOS for different times, and then stimulated with TNF-alpha for 4h. The results show that pre-treating ECs with NACOS inhibited the TNF-alpha-induced E-selectin expression in a dose- and time-dependent manner. This NACOS-mediated inhibition in E-selectin expression was regulated at the transcriptional level, but not due to changes in mRNA stability. Stimulation of ECs with TNF-alpha-induced rapid increases in the phosphorylation of their mitogen-activated protein kinases (MAPKs) [extracellular signal-regulated kinase (ERK), c-Jun-NH2-terminal kinase (JNK), and p38 MAPK]; the inhibitor for JNK (i.e., SP600125), but not those for ERK (i.e., PD98059) and p38 MAPK (i.e., SB203580), attenuated this TNF-alpha-induced E-selectin expression. Pre-treating ECs with NACOS inhibited the TNF-alpha-induced JNK activation, suggesting that JNK was involved in the inhibitory effect of NACOS on TNF-alpha-induced E-selectin expression. Pre-treating ECs with NACOS inhibited the TNF-alpha-induced p65 and p50 mRNA expressions. Gel shifting and chromatin immunoprecipitation assays showed that NACOS blocked the TNF-alpha-induced increases in the binding activity and in vivo promoter binding of nuclear factor-kappaB (NF-kappaB) in ECs. Our findings provide a molecular mechanism by which NACOS inhibit TNF-alpha-induced E-selectin expression in ECs, and a basis for using NACOS in pharmaceutical therapy against inflammation. SN - 0142-9612 UR - https://www.unboundmedicine.com/medline/citation/17126899/The_inhibition_of_TNF_alpha_induced_E_selectin_expression_in_endothelial_cells_via_the_JNK/NF_kappaB_pathways_by_highly_N_acetylated_chitooligosaccharides_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0142-9612(06)00952-5 DB - PRIME DP - Unbound Medicine ER -