Inhibiting Mer receptor tyrosine kinase suppresses STAT1, SOCS1/3, and NF-κB activation and enhances inflammatory responses in lipopolysaccharide-induced …

YJ Lee, JY Han, J Byun, HJ Park… - Journal of leukocyte …, 2012 - academic.oup.com
YJ Lee, JY Han, J Byun, HJ Park, EM Park, YH Chong, MS Cho, JL Kang
Journal of leukocyte biology, 2012academic.oup.com
Mer signaling participates in a novel inhibitory pathway in TLR activation. The purpose of the
present study was to examine the role of Mer signaling in the down-regulation of TLR4
activation-driven immune responses in mice, it-treated with LPS, using the specific Mer-
blocking antibody. At 4 h and 24 h after LPS treatment, expression of Mer protein in alveolar
macrophages and lung tissue decreased, sMer in BALF increased significantly, and Mer
activation increased. Pretreatment with anti-Mer antibody did not influence the protein levels …
Abstract
Mer signaling participates in a novel inhibitory pathway in TLR activation. The purpose of the present study was to examine the role of Mer signaling in the down-regulation of TLR4 activation-driven immune responses in mice, i.t.-treated with LPS, using the specific Mer-blocking antibody. At 4 h and 24 h after LPS treatment, expression of Mer protein in alveolar macrophages and lung tissue decreased, sMer in BALF increased significantly, and Mer activation increased. Pretreatment with anti-Mer antibody did not influence the protein levels of Mer and sMer levels. Anti-Mer antibody significantly reduced LPS-induced Mer activation, phosphorylation of Akt and FAK, STAT1 activation, and expression of SOCS1 and -3. Anti-Mer antibody enhanced LPS-induced inflammatory responses, including activation of the NF-κB pathway; the production of TNF-α, IL-1β, and MIP-2 and MMP-9 activity; and accumulation of inflammatory cells and the total protein levels in BALF. These results indicate that Mer plays as an intrinsic feedback inhibitor of the TLR4- and inflammatory mediator-driven immune responses during acute lung injury.
Oxford University Press