Extracellular RNA facilitates hypoxia-induced leukocyte adhesion and infiltration in the lung through TLR3-IFN-γ-STAT1 signaling pathway

European Journal of Immunology
Indranil BiswasGausal A Khan

Abstract

Endogenous ligands released from dying cells, including extracellular RNA (eRNA), cause TLR activation, which is associated with inflammation and vascular diseases. However, the importance of this response in acute hypoxia (AH) remains unexplored. Here, we observed eRNA-mediated TLR3 activation during exposure of mice to AH in the absence of exogenous viral stimuli. RNaseA treatment diminished AH-induced expression of IFN and cell adhesion molecules (CAMs) and myeloid cell infiltration in the lung, and TLR3 gene silencing or neutralization with antibodies markedly attenuated AH- or poly I:C-induced IFN and CAM expression and leukocyte adhesion (LA) and myeloid cell infiltration in the lung. However, RNaseA treatment or TLR3 gene silencing failed to alter AH-induced cell death and proliferation in lung vasculature. Furthermore, IFN-γ--but not IFN-α--regulated AH-induced CAM expression and LA. Treatment with RNaseA, TLR3 siRNA, neutralizing antibodies, or a STAT1 inhibitor substantially decreased AH- and poly I:C-induced STAT1 phosphorylation, CAM expression, and myeloid cell infiltration, suggesting a central role for STAT1 phosphorylation in AH-induced LA and infiltration. We conclude that eRNA activates TLR3 and facilitates, t...Continue Reading

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Citations

Nov 5, 2019·Frontiers in Molecular Neuroscience·Katharina TielkingRan Xu
Jan 5, 2021·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Muhammad Ali HaidarFiras Kobeissy
Jan 5, 2021·Frontiers in Cell and Developmental Biology·Klaus T PreissnerElisabeth Deindl
Nov 6, 2020·Journal of Inflammation Research·Indranil Biswas, Gausal A Khan
Apr 21, 2021·Indian Journal of Clinical Biochemistry : IJCB·Anmol GoyalIsha Rani
Dec 10, 2021·PloS One·Saumya BhagatGausal A Khan

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