TY - JOUR
T1 - Macrophage migration inhibitory factor in acute lung injury
T2 - expression, biomarker, and associations
AU - Gao, Li
AU - Flores, Carlos
AU - Fan-Ma, Shwu
AU - Miller, Edmund J.
AU - Moitra, Jaideep
AU - Moreno, Liliana
AU - Wadgaonkar, Raj
AU - Simon, Brett
AU - Brower, Roy
AU - Sevransky, Jonathan
AU - Tuder, Rubin M.
AU - Maloney, James P.
AU - Moss, Marc
AU - Shanholtz, Carl
AU - Yates, C. Ryan
AU - Meduri, Gianfranco Umberto
AU - Ye, Shui Q.
AU - Barnes, Kathleen C.
AU - Garcia, Joe G.N.
N1 - Funding Information:
Supported in part by the National Heart Lung Blood Institute HopGene PGA Program in Genomic Applications (NIH HL 69084, JGNG PI), Program Project Grant (HL 58064, JGNG), the Specialized Center for Clinical Oriented Research (SCCOR) award (HL 73994), and the Lowell T. Coggeshall endowment at the University of Chicago (J.G.N.G). Supported also in part by NIH T32 training grant (to L.G.), the Fundacion Canaria Dr. Manuel Morales (C.F.), and the Mary Beryl Patch Turnbull Scholar Program (K.C.B.).
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.trsl.2007.02.007
DO - 10.1016/j.trsl.2007.02.007
M3 - Article
C2 - 17585860
AN - SCOPUS:34250656192
SN - 1931-5244
VL - 150
SP - 18
EP - 29
JO - Translational Research
JF - Translational Research
IS - 1
ER -