title: Kruppel-like factor 2 is a transcriptional regulator of chronic and acute inflammation.
abstract: Although myeloid cell activation is requisite for an optimal innate immune response, this process must be tightly controlled to prevent collateral host tissue damage. Kruppel-like factor 2 (KLF2) is a potent regulator of myeloid cell proinflammatory activation. As an approximately 30% to 50% reduction in KLF2 levels has been observed in human subjects with acute or chronic inflammatory disorders, we studied the biological response to inflammation in KLF2(+/-) mice. Herein, we show that partial deficiency of KLF2 modulates the in vivo response to acute (sepsis) and subacute (skin) inflammatory challenge. Mechanistically, we link the anti-inflammatory effects of KLF2 to the inhibition of NF-κB transcriptional activity. Collectively, the observations provide biologically relevant insights into KLF2-mediated modulation of these inflammatory processes that could potentially be manipulated for therapeutic gain.
authors.affiliation: Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, Cleveland, Ohio; Division of Hematology and Oncology, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Lalitha
authors.initials: L
authors.lastname: Nayak
authors.forename: Lediana
authors.initials: L
authors.lastname: Goduni
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takami
authors.forename: Nikunj
authors.initials: N
authors.lastname: Sharma
authors.forename: Parul
authors.initials: P
authors.lastname: Kapil
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
authors.forename: Ganapati H
authors.initials: GH
authors.lastname: Mahabeleshwar
mesh_terms: D000208:Acute Disease; D000818:Animals; D002351:Carrageenan; D002460:Cell Line; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004487:Edema / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D057898:Hemizygote; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018805:Sepsis / Q000235:genetics / Q000473:pathology; D012867:Skin / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D002351:Carrageenan