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Identification of novel innate immune genes by transcriptional profiling of macrophages stimulated with TLR ligands.

Publication ,  Journal Article
Yang, IV; Jiang, W; Rutledge, HR; Lackford, B; Warg, LA; De Arras, L; Alper, S; Schwartz, DA; Pisetsky, DS
Published in: Mol Immunol
September 2011

Toll-like receptors (TLRs) are key receptors in innate immunity and trigger responses following interaction with pathogen-associated molecular patterns (PAMPs). TLR3, TLR4 and TLR9 recognize double stranded RNA, lipopolysaccharide (LPS) and CpG DNA, respectively. These receptors differ importantly in downstream adaptor molecules. TLR4 signals through MyD88 and TRIF; in contrast, the TLR3 pathway involves only TRIF while TLR9 signals solely through MyD88. To determine how differences in downstream signaling could influence gene expression in innate immunity, gene expression patterns were determined for the RAW264.7 macrophage cell line stimulated with LPS, poly (I:C), or CpG DNA. Gene expression profiles 6 and 24h post-stimulation were analyzed to determine genes, pathways and transcriptional networks induced. As these experiments showed, the number and extent of genes expressed varied with stimulus. LPS and poly (I:C) induced an abundant array of genes in RAW264.7 cells at 6h and 24h following treatment while CpG DNA induced many fewer. By analyzing data for networks and pathways, we prioritized differentially expressed genes with respect to those common to the three TLR ligands as well as those shared by LPS and poly (I:C) but not CpG DNA. The importance of changes in gene expression was demonstrated by experiments indicating that RNA interference-mediated inhibition of two genes identified in this analysis, PLEC1 and TPST1, reduced IL-6 production by J774A.1 and RAW264.7 macrophages stimulated with LPS. Together, these findings delineate macrophage gene response patterns induced by different PAMPs and identify new genes that have not previously been implicated in innate immunity.

Duke Scholars

Published In

Mol Immunol

DOI

EISSN

1872-9142

Publication Date

September 2011

Volume

48

Issue

15-16

Start / End Page

1886 / 1895

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Toll-Like Receptors
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA Interference
  • Poly I-C
  • Oligonucleotide Array Sequence Analysis
  • Mice
  • Macrophages
  • Lipopolysaccharides
  • Ligands
 

Citation

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Yang, I. V., Jiang, W., Rutledge, H. R., Lackford, B., Warg, L. A., De Arras, L., … Pisetsky, D. S. (2011). Identification of novel innate immune genes by transcriptional profiling of macrophages stimulated with TLR ligands. Mol Immunol, 48(15–16), 1886–1895. https://doi.org/10.1016/j.molimm.2011.05.015
Yang, Ivana V., Weiwen Jiang, Holly R. Rutledge, Brad Lackford, Laura A. Warg, Lesly De Arras, Scott Alper, David A. Schwartz, and David S. Pisetsky. “Identification of novel innate immune genes by transcriptional profiling of macrophages stimulated with TLR ligands.Mol Immunol 48, no. 15–16 (September 2011): 1886–95. https://doi.org/10.1016/j.molimm.2011.05.015.
Yang IV, Jiang W, Rutledge HR, Lackford B, Warg LA, De Arras L, et al. Identification of novel innate immune genes by transcriptional profiling of macrophages stimulated with TLR ligands. Mol Immunol. 2011 Sep;48(15–16):1886–95.
Yang, Ivana V., et al. “Identification of novel innate immune genes by transcriptional profiling of macrophages stimulated with TLR ligands.Mol Immunol, vol. 48, no. 15–16, Sept. 2011, pp. 1886–95. Pubmed, doi:10.1016/j.molimm.2011.05.015.
Yang IV, Jiang W, Rutledge HR, Lackford B, Warg LA, De Arras L, Alper S, Schwartz DA, Pisetsky DS. Identification of novel innate immune genes by transcriptional profiling of macrophages stimulated with TLR ligands. Mol Immunol. 2011 Sep;48(15–16):1886–1895.
Journal cover image

Published In

Mol Immunol

DOI

EISSN

1872-9142

Publication Date

September 2011

Volume

48

Issue

15-16

Start / End Page

1886 / 1895

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Toll-Like Receptors
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA Interference
  • Poly I-C
  • Oligonucleotide Array Sequence Analysis
  • Mice
  • Macrophages
  • Lipopolysaccharides
  • Ligands