title: The myeloid transcription factor KLF2 regulates the host response to polymicrobial infection and endotoxic shock.
abstract: Precise control of myeloid cell activation is required for optimal host defense. However, this activation process must be under exquisite control to prevent uncontrolled inflammation. Herein, we identify the Kruppel-like transcription factor 2 (KLF2) as a potent regulator of myeloid cell activation in vivo. Exposure of myeloid cells to hypoxia and/or bacterial products reduced KLF2 expression while inducing hypoxia inducible factor-1α (HIF-1α), findings that were recapitulated in human septic patients. Myeloid KLF2 was found to be a potent inhibitor of nuclear factor-kappaB (NF-κB)-dependent HIF-1α transcription and, consequently, a critical determinant of outcome in models of polymicrobial infection and endotoxemia. Collectively, these observations identify KLF2 as a tonic repressor of myeloid cell activation in vivo and an essential regulator of the innate immune system.
authors.affiliation: Case Cardiovascular Research Institute, Department of Medicine, Harrington-McLaughlin Heart and Vascular Institute, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors.forename: Ganapati H
authors.initials: GH
authors.lastname: Mahabeleshwar
authors.forename: Daiji
authors.initials: D
authors.lastname: Kawanami
authors.forename: Nikunj
authors.initials: N
authors.lastname: Sharma
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takami
authors.forename: Guangjin
authors.initials: G
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Lalitha
authors.initials: L
authors.lastname: Nayak
authors.forename: Darwin
authors.initials: D
authors.lastname: Jeyaraj
authors.forename: Robert
authors.initials: R
authors.lastname: Grealy
authors.forename: Mary
authors.initials: M
authors.lastname: White
authors.forename: Ross
authors.initials: R
authors.lastname: McManus
authors.forename: Thomas
authors.initials: T
authors.lastname: Ryan
authors.forename: Patrick
authors.initials: P
authors.lastname: Leahy
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lin
authors.forename: Saptarsi M
authors.initials: SM
authors.lastname: Haldar
authors.forename: G Brandon
authors.initials: GB
authors.lastname: Atkins
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
authors.forename: Jerry B
authors.initials: JB
authors.lastname: Lingrel
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D002460:Cell Line; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology; D007113:Immunity, Innate; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B