Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes

Hiranmoy Das, Ajay Kumar, Zhiyong Lin, Willmar D. Patino, Paul M. Hwang, Mark W. Feinberg, Pradip K. Majumder, Mukesh K. Jain

Research output: Contribution to journalArticle

Abstract

The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, KLF2 inhibits the transcriptional activity of both NF-κB and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation.

Original languageEnglish (US)
Pages (from-to)6653-6658
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number17
DOIs
StatePublished - Apr 25 2006
Externally publishedYes

Fingerprint

Kruppel-Like Transcription Factors
Monocytes
Cytokines
Carrageenan
Transcription Factor AP-1
Phagocytosis
Chemokines
Small Interfering RNA
Coronary Artery Disease
Edema
Gene Expression

Keywords

  • Activator protein 1
  • Inflammation
  • NF-κB
  • Transcription
  • Transcriptional factor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes. / Das, Hiranmoy; Kumar, Ajay; Lin, Zhiyong; Patino, Willmar D.; Hwang, Paul M.; Feinberg, Mark W.; Majumder, Pradip K.; Jain, Mukesh K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 17, 25.04.2006, p. 6653-6658.

Research output: Contribution to journalArticle

Das, H, Kumar, A, Lin, Z, Patino, WD, Hwang, PM, Feinberg, MW, Majumder, PK & Jain, MK 2006, 'Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes', Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 17, pp. 6653-6658. https://doi.org/10.1073/pnas.0508235103
Das, Hiranmoy ; Kumar, Ajay ; Lin, Zhiyong ; Patino, Willmar D. ; Hwang, Paul M. ; Feinberg, Mark W. ; Majumder, Pradip K. ; Jain, Mukesh K. / Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 17. pp. 6653-6658.
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