Literature DB >> 20652722

Toll-like receptor 4 signaling in dysfunction of cardiac microvascular endothelial cells under hypoxia/reoxygenation.

Zheng Zhang1, Weijie Li, Dongdong Sun, Li Zhao, Rongqing Zhang, Yabin Wang, Xuan Zhou, Haichang Wang, Feng Cao.   

Abstract

OBJECTIVE: This study was designed to detect the role of Toll-like receptor 4 (TLR4) signaling in the dysfunction of cardiac microvascular endothelial cells (CMECs) after hypoxia/reoxygenation (H/R).
METHODS: The cell viability of CMECs was measured by MTT assay. The migration of CMECs was detected by cell scratch wound assay. The expressions of TLR4, nuclear factor-kappa B (NF-κB) and eNOS were analyzed by Western blot. Secretions of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were determined by NO detection kit and ELISA.
RESULTS: Lipopolysaccharide (LPS) incubation increased the expressions of TLR4, NF-κB, IL-6 and TNF-α in CMECs (P < 0.05 vs. control). The CMECs after H/R injury had impaired cell viability (P < 0.01 vs. control) and migration ability (P < 0.05 vs. control). Moreover, the expressions of TLR4, NF-κB, IL-6 and TNF-α were elevated after H/R in CMECs (P < 0.01 vs. control), while NO and the eNOS expression were significantly decreased. In contrast, administration of the TLR4-neutralizing antibody MTS510 prior to H/R injury down-regulated the expressions of IL-6 and TNF-α and attenuated the dysfunction of CMECs.
CONCLUSION: TLR4 and its signaling components can be activated by LPS and H/R in CMECs. Blocking the TLR4 signal pathway before H/R injury attenuates CMEC dysfunction.

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Year:  2010        PMID: 20652722     DOI: 10.1007/s00011-010-0232-2

Source DB:  PubMed          Journal:  Inflamm Res        ISSN: 1023-3830            Impact factor:   4.575


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