Macrophage migration inhibitory factor in acute lung injury: expression, biomarker, and associations.
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.
Gao
Li
L
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Flores
Carlos
C
Fan-Ma
Shwu
S
Miller
Edmund J
EJ
Moitra
Jaideep
J
Moreno
Liliana
L
Wadgaonkar
Raj
R
Simon
Brett
B
Brower
Roy
R
Sevransky
Jonathan
J
Tuder
Rubin M
RM
Maloney
James P
JP
Moss
Marc
M
Shanholtz
Carl
C
Yates
C Ryan
CR
Meduri
Gianfranco Umberto
GU
Ye
Shui Q
SQ
Barnes
Kathleen C
KC
Garcia
Joe G N
JG
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
D015415:Biomarkers; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse