title: Macrophage migration inhibitory factor in acute lung injury: expression, biomarker, and associations.
abstract: The macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine central to the response to endotoxemia, is a putative biomarker in acute lung injury (ALI). To explore MIF as a molecular target and candidate gene in ALI, the MIF gene and protein expression were examined in murine and canine models of ALI (high tidal volume mechanical ventilation, endotoxin exposure) and in patients with either sepsis or sepsis-induced ALI. MIF gene expression and protein levels were significantly increased in each ALI model, with serum MIF levels significantly higher in patients with either sepsis or ALI compared with healthy controls (African- and European-descent). The association of 8 MIF gene polymorphisms (single-nucleotide polymorphisms (SNPs)) (within a 9.7-kb interval on chromosome 22q11.23) with the development of sepsis and ALI in European-descent and African-descent populations was studied next. Genotyping in 506 DNA samples (sepsis patients, sepsis-associated ALI patients, and healthy controls) revealed haplotypes located in the 3' end of the MIF gene, but not individual SNPs, associated with sepsis and ALI in both populations. These data, generated via functional genomic and genetic approaches, suggest that MIF is a relevant molecular target in ALI.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Carlos
authors.initials: C
authors.lastname: Flores
authors.forename: Shwu
authors.initials: S
authors.lastname: Fan-Ma
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Miller
authors.forename: Jaideep
authors.initials: J
authors.lastname: Moitra
authors.forename: Liliana
authors.initials: L
authors.lastname: Moreno
authors.forename: Raj
authors.initials: R
authors.lastname: Wadgaonkar
authors.forename: Brett
authors.initials: B
authors.lastname: Simon
authors.forename: Roy
authors.initials: R
authors.lastname: Brower
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sevransky
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
authors.forename: James P
authors.initials: JP
authors.lastname: Maloney
authors.forename: Marc
authors.initials: M
authors.lastname: Moss
authors.forename: Carl
authors.initials: C
authors.lastname: Shanholtz
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Yates
authors.forename: Gianfranco Umberto
authors.initials: GU
authors.lastname: Meduri
authors.forename: Shui Q
authors.initials: SQ
authors.lastname: Ye
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood* / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012128:Respiratory Distress Syndrome / Q000208:ethnology / Q000276:immunology* / Q000378:metabolism*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D015415:Biomarkers; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse