The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation.
The adipocyte fatty acid-binding protein aP2 regulates systemic glucose and lipid metabolism. We report that aP2, in addition to being abundantly expressed by adipocytes, is also expressed by human airway epithelial cells and shows a striking upregulation following stimulation of epithelial cells with the Th2 cytokines IL-4 and IL-13. Regulation of aP2 mRNA expression by Th2 cytokines was highly dependent on STAT6, a transcription factor with a major regulatory role in allergic inflammation. We examined aP2-deficient mice in a model of allergic airway inflammation and found that infiltration of leukocytes, especially eosinophils, into the airways was highly dependent on aP2 function. T cell priming was unaffected by aP2 deficiency, suggesting that aP2 was acting locally within the lung, and analysis of bone marrow chimeras implicated non-hematopoietic cells, most likely bronchial epithelial cells, as the site of action of aP2 in allergic airway inflammation. Thus, aP2 regulates allergic airway inflammation and may provide a link between fatty acid metabolism and asthma.
Shum
Bennett O V
BO
Immunology and Inflammation Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
Mackay
Charles R
CR
Gorgun
Cem Z
CZ
Frost
Melinda J
MJ
Kumar
Rakesh K
RK
Hotamisligil
Gökhan S
GS
Rolph
Michael S
MS
D016475:3T3 Cells; D017667:Adipocytes / Q000276:immunology / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000502:physiology; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000503:physiopathology*; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020545:Respiratory Mucosa / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic
C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4