Functional genomics of silencing TREM-1 on TLR4 signaling in macrophages

M. Ornatowska, A. C. Azim, X. Wang, J. W. Christman, L. Xiao, M. Joo, R. T. Sadikot

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently discovered molecule that is expressed on the cell surface of monocytes and neutrophils. Engagement of TREM-1 triggers synthesis of proinflammatory cytokines in response to microbes, but the extent and mechanism by which TREM-1 modulates the inflammatory response is poorly defined. In the present study, we investigated the functional effects of blocking TREM-1 on the Toll-like receptor (TLR)4-mediated signaling pathway in macrophages. By transfecting cells with small hairpin interfering RNA molecules to TREM-1 (shRNA), we confirmed that TREM-1 mRNA and protein expression was greatly attenuated in RAW cells in response to treatment with LPS. PCR array for genes related to or activated by the TLR pathway revealed that although the expression of TLR4 itself was not significantly altered by silencing of TREM-1, expression of several genes, including MyD88, CD14, IκBα, IL-1β, MCP-1, and IL-10 was significantly attenuated in the TREM-1 knockdown cells in response to treatment with LPS. These data indicate that expression of TREM-1 modulates the TLR signaling in macrophages by altering the expression of both adaptor and effector proteins that are critical to the endotoxin response.

Original languageEnglish (US)
Pages (from-to)L1377-L1384
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume293
Issue number6
DOIs
StatePublished - Dec 2007
Externally publishedYes

Keywords

  • Toll-like receptor
  • Triggering receptor expressed on myeloid cells 1

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint

Dive into the research topics of 'Functional genomics of silencing TREM-1 on TLR4 signaling in macrophages'. Together they form a unique fingerprint.

Cite this