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Activation of vascular Toll‐like receptor 3 induces phosphorylation of caldesmon via ERK1/2 pathway (1065.12)
Author(s) -
CarrilloSepulveda Maria Alicia,
Hardigan Trevor,
Webb R. Clinton
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1065.12
Subject(s) - phosphorylation , vascular smooth muscle , tlr3 , caldesmon , mapk/erk pathway , endocrinology , medicine , myosin light chain kinase , chemistry , signal transduction , microbiology and biotechnology , biology , receptor , innate immune system , biochemistry , toll like receptor , smooth muscle , enzyme , calmodulin
TLR3, a pattern‐recognition receptor of the innate immune system, is constitutively expressed in vascular smooth muscle cells (VSMC) and has been showed to be functional in the vascular system; however its role in contraction remains unknown. Caldesmon (CaD) is a potent and versatile regulatory protein that play crucial role in contractility of smooth muscle. We hypothesized that TLR3 contributes to contractile events in VSMC by phosphorylation of CaD in Ser789. Phosphorylation of myosin light chain (pMLC), marker of contraction, increased by 65% in mouse C57bl/6 aortic smooth muscle cells (ASMC) stimulated with TLR3 agonist polyinosine polycytidylic acid (Poly I:C) (10 μg/mL, 60 min). This effect was accompanied by increased phosphorylation of CaD on Ser789 (3 fold versus control unstimulated ASMC) as well as significantly activation of mitogen‐activated protein/extracellular signal‐regulated kinase (ERK1/2). Pre‐treatment with PD98059 (50μM, 30 min), ERK1/2 inhibitor, abolished Poly I:C‐mediated phosphorylation of CaD. Interestingly, chronic treatment with Poly I:C for 24 hours downregulated by 40% TLR3 expression in ASMC. The present results showed that activation of TLR3 in VSMC causes ERK1/2‐mediated phosphorylation of CaD, thereby contributing to augmented contraction and consequently to development of vascular dysfunction. Our data provide the first functional assessment of the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction. Grant Funding Source : AHA 13POST14690026