Pathogen recognition by toll-like receptor 2 activates Weibel-Palade body exocytosis in human aortic endothelial cells

Takeshi Into, Yosuke Kanno, Jun Ichi Dohkan, Misako Nakashima, Megumi Inomata, Ken Ichiro Shibata, Charles J. Lowenstein, Kenji Matsushita

Research output: Contribution to journalArticlepeer-review

Abstract

The endothelial cell-specific granule Weibel-Palade body releases vasoactive substances capable of modulating vascular inflammation. Although innate recognition of pathogens by Toll-like receptors (TLRs) is thought to play a crucial role in promotion of inflammatory responses, the molecular basis for early-phase responses of endothelial cells to bacterial pathogens has not fully been understood. We here report that human aortic endothelial cells respond to bacterial lipoteichoic acid (LTA) and synthetic bacterial lipopeptides, but not lipopolysaccharide or peptidoglycan, to induce Weibel-Palade body exocytosis, accompanied by release or externalization of the storage components von Willebrand factor and P-selectin. LTA could activate rapid Weibel-Palade body exocytosis through a TLR2- and MyD88-dependent mechanism without de novo protein synthesis. This process was at least mediated through MyD88-dependent phosphorylation and activation of phospholipase Cγ. Moreover, LTA activated interleukin-1 receptor-associated kinase-1-dependent delayed exocytosis with de novo protein synthesis and phospholipase Cγ-dependent activation of the NF-κB pathway. Increased TLR2 expression by transfection or interferon-γ treatment increased TLR2-mediated Weibel-Palade body exocytosis, whereas reduced TLR2 expression under laminar flow decreased the response. Thus, we propose a novel role for TLR2 in induction of a primary proinflammatory event in aortic endothelial cells through Weibel-Palade body exocytosis, which may be an important step for linking innate recognition of bacterial pathogens to vascular inflammation.

Original languageEnglish (US)
Pages (from-to)8134-8141
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number11
DOIs
StatePublished - Mar 16 2007

ASJC Scopus subject areas

  • Biochemistry

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