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Role of Toll‐like receptors in ischemic stroke induced endothelial cell dysfunction
Author(s) -
Tiwari Samata,
Mattson Mark P,
Arumugam Thiruma V
Publication year - 2008
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.22.1_supplement.716.12
Subject(s) - tlr2 , signal transduction , microbiology and biotechnology , receptor , toll like receptor , tlr4 , endothelial stem cell , signal transducing adaptor protein , transcription factor , biology , endothelial dysfunction , immunology , medicine , innate immune system , endocrinology , in vitro , gene , biochemistry
Toll‐like receptors (TLRs) regulate host responses to pathogens and inflammatory responses. Activation of TLRs initiates signal transduction cascades involving kinases and transcription factors activator protein‐1 and NF‐kappa B. Recently studies have shown that TLR2 and −4 may play a role in ischemic stroke induced brain injury. Our recent findings showed that TLR2 and −4 are expressed in cerebral cortical neurons where their levels and downstream signaling via JNK are increased in response to energy deprivation in cell culture and ischemia in vivo. Here we use human microvascular endothelial cells (HMECs), mouse brain endothelial cells (MBECs) and in vivo models of ischemic stroke to elucidate roles of endothelial TLR2, −3 and −4 signaling in ischemic stroke induced endothelial dysfunction. Preliminary data shows that TLR2, −3 and −4 mRNA expression were increased during the first few hours in glucose deprivation (GD) and oxygen and glucose deprivation (OGD) conditions in both HMECs and MBECs. We also observed increased levels of TLR signaling adaptor molecule MYD88 mRNA in response to GD and OGD. Immunoblot analysis also showed increased expression of TLR proteins and MyD88 in response to OGD in MBECs. Preliminary results indicate a role for endothelial TLR signaling in pathogenesis of stroke. Research Support: TTUHSC School of Pharmacy Start up Fund.