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

Ye Ji Lee, Ji Young Han, Jiyeon Byun, Hyun Jeong Park, Eun Mi Park, Young Hae Chong, Min Sun Cho, Jihee Lee Kang

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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.

Original languageEnglish
Pages (from-to)921-932
Number of pages12
JournalJournal of Leukocyte Biology
Volume91
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Alveolar macrophages
  • Inflammatory mediators
  • Mer signaling
  • Pulmonary inflammation
  • Soluble Mer

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