NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 Agonists

Objective. To investigate the expression of NOD2 in human VSMCs, its role in the production of inflammatory cytokines in VSMC and the possible interaction of NOD2-mediated signaling pathway with those mediated by TLR2 and TLR4. Methods. Human coronary artery smooth muscle cells were stimulated with...

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Main Authors: Jinghua Sun, Yanchun Ding
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/2012/607157
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author Jinghua Sun
Yanchun Ding
author_facet Jinghua Sun
Yanchun Ding
author_sort Jinghua Sun
collection DOAJ
description Objective. To investigate the expression of NOD2 in human VSMCs, its role in the production of inflammatory cytokines in VSMC and the possible interaction of NOD2-mediated signaling pathway with those mediated by TLR2 and TLR4. Methods. Human coronary artery smooth muscle cells were stimulated with NOD2 agonist MDP alone or in combination with either TLR2 agonist PAM3 or TLR4 agonist LPSs. The mRNA expression of NOD2 and FGF-2 were measured by RT-PCR. The concentration of IL-8 and TNF-α in the culture supernatants was determined by ELISA. VSMC proliferation ability was analyzed by MTT assay. Results. MDP up regulated the expression of NOD2 mRNA in VSMC in a time-dependent manner, up regulated the expression of FGF-2 mRNA in VSMC, induced the production of IL-8 and TNF-α, and promoted the proliferation of VSMC. Additionally, MDP synergied with LPS and PAM3 to promote the proliferation of VSMC and induce the production of IL-8 and TNF-α. Conclusion. The activation of NOD2-mediated innate immune signaling pathway can increase the proliferation ability of VSMC and induce the production of inflammatory cytokines in VSMC. It is also shown a synergistic effect with TLR2- and TLR4-mediated signaling pathways in this process.
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spelling doaj-art-6b186db1b23e490f8a072e91f894ed212025-08-20T02:23:56ZengWileyThe Scientific World Journal1537-744X2012-01-01201210.1100/2012/607157607157NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 AgonistsJinghua Sun0Yanchun Ding1Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, ChinaObjective. To investigate the expression of NOD2 in human VSMCs, its role in the production of inflammatory cytokines in VSMC and the possible interaction of NOD2-mediated signaling pathway with those mediated by TLR2 and TLR4. Methods. Human coronary artery smooth muscle cells were stimulated with NOD2 agonist MDP alone or in combination with either TLR2 agonist PAM3 or TLR4 agonist LPSs. The mRNA expression of NOD2 and FGF-2 were measured by RT-PCR. The concentration of IL-8 and TNF-α in the culture supernatants was determined by ELISA. VSMC proliferation ability was analyzed by MTT assay. Results. MDP up regulated the expression of NOD2 mRNA in VSMC in a time-dependent manner, up regulated the expression of FGF-2 mRNA in VSMC, induced the production of IL-8 and TNF-α, and promoted the proliferation of VSMC. Additionally, MDP synergied with LPS and PAM3 to promote the proliferation of VSMC and induce the production of IL-8 and TNF-α. Conclusion. The activation of NOD2-mediated innate immune signaling pathway can increase the proliferation ability of VSMC and induce the production of inflammatory cytokines in VSMC. It is also shown a synergistic effect with TLR2- and TLR4-mediated signaling pathways in this process.http://dx.doi.org/10.1100/2012/607157
spellingShingle Jinghua Sun
Yanchun Ding
NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 Agonists
The Scientific World Journal
title NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 Agonists
title_full NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 Agonists
title_fullStr NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 Agonists
title_full_unstemmed NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 Agonists
title_short NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 Agonists
title_sort nod2 agonist promotes the production of inflammatory cytokines in vsmc in synergy with tlr2 and tlr4 agonists
url http://dx.doi.org/10.1100/2012/607157
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AT yanchunding nod2agonistpromotestheproductionofinflammatorycytokinesinvsmcinsynergywithtlr2andtlr4agonists