These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Critical role of toll-like receptor 4 in hypoxia-inducible factor 1α activation during trauma/hemorrhagic shocky induced acute lung injury after lymph infusion in mice.
    Author: Jiang H, Hu R, Sun L, Chai D, Cao Z, Li Q.
    Journal: Shock; 2014 Sep; 42(3):271-8. PubMed ID: 24978883.
    Abstract:
    AB The nuclear transcription factor hypoxia-inducible factor 1[alpha] (HIF-1α) is a key regulator of gene expression under hypoxic and inflammatory conditions. The germline-encoded pattern recognition receptor toll-like receptor 4 (TLR4) recognizes molecular motifs shared by large groups of microorganisms as well as by endogenous ligands released from stressed and/or injured tissues. We have previously demonstrated that local inhibition of HIF-1α ameliorates lung injury induced by trauma/hemorrhagic shock (T/HS) in rats. In the current study, we directly determined the role of TLR4 in HIF-1α activation during T/HS-induced acute lung injury in mice. C3H/HeJ mice that harbor a TLR4 mutation and wild-type (WT) mice were infused T/HS or trauma/sham shock (T/SS) lymph from Sprague-Dawley rats. Evans blue dye lung permeability, lung water content, myeloperoxidase levels, and lung histological analysis confirmed that TLR4-deficient mice are resistant to lung injury after T/HS lymph infusion. Lungs from WT and TLR4mut mice after T/SS lymph infusion expressed negligible levels of HIF-1α. The induction of HIF-1α in lung homogenates from TLR4mut mice after T/HS or T/HS lymph infusion was markedly reduced as compared with their WT counterparts but remained elevated as compared with TLR4mut mice after T/SS lymph infusion. Endothelial cells from TLR4mut mice and silence of TLR4 in cells from WT mice showed a remarkable reduction of HIF-1α on T/HS lymph stimulation. Blocking of nuclear factor-κB activity by SN50 or Bay 11-7085 in WT cells diminished T/HS lymph-induced HIF-1α accumulation when compared with T/SS lymph incubation. Thus, our data suggest that TLR4 activation by T/HS is necessary for T/HS-induced lung injury and an augmented pulmonary HIF-1α response, which will provide more insights into the pathogenesis of shock-induced acute lung injury and identify potential therapeutic targets.
    [Abstract] [Full Text] [Related] [New Search]