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

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 LPSmediated 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-B and activator protein 1, in part by means of recruitment of transcriptional coactivator p300͞CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation.inflammation ͉ transcription ͉ transcriptional factor ͉ NF-B ͉ activator protein 1

A Myeloid Hypoxia-inducible Factor 1α-Krüppel-like Factor 2 Pathway Regulates Gram-positive Endotoxin-mediated Sepsis

“…In this regard, the identification of KLF2 is particularly noteworthy. Previous studies from our group were first to implicate KLF2 as an inhibitor of myeloid proinflammatory activation (23,24). More recently, we showed that myeloid-specific deletion of KLF2 led to spontaneous low-level myeloid activation even under basal conditions (24).…”

“…Krüppel-like factor 2 (KLF2) was initially identified by the Lingrel laboratory and termed lung Krüppel-like factor because of its high level in lung tissues (22). In the context of myeloid cell biology, our group identified KLF2 as a negative regulator of myeloid cell activation (23). KLF2 overexpression was found to attenuate LPSinduced expression of cytokines and chemokines through inhibiting transcriptional activity of NF-B and activator protein 1 (AP-1).…”

p53 and p16INK4A independent induction of senescence by chromatin-dependent alteration of S-phase progression

“…Key DDR-signalling components are the protein kinases Ataxia-telangiectasia-mutated (ATM) and Ataxia-telangiectasia and Rad3-related (ATR), which activate the downstream kinases CHK2 and CHK1, respectively, leading to a cell cycle arrest 17 . Furthermore, acetylation of histone H3 on lysine 56 (H3K56) has recently been shown to be mediated by p300 HAT activity and to have a critical role in packaging DNA into chromatin for DNA replication and repair [18][19][20][21][22] . We therefore investigated whether senescence induced by p300 HAT inhibition was also dependent on the activation of DDR.…”

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

“…This transcription factor, also called lung KLF, belongs to the SP-1 zinc-finger transcription factor 46 . KLF2 exerts an anti-inflammatory activity in endothelial cells, monocytes and epithelial cells [47][48][49] . Our studies report for the first time the implication of a transcription factor of the KLF family in sPLA2-IIA transcription.…”