The adipocyte fatty acid–binding protein aP2 is required in allergic airway inflammation
Bennett O.V. Shum, … , Gökhan S. Hotamisligil, Michael S. Rolph
Bennett O.V. Shum, … , Gökhan S. Hotamisligil, Michael S. Rolph
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2183-2192. https://doi.org/10.1172/JCI24767.
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The adipocyte fatty acid–binding protein aP2 is required in allergic airway inflammation

Abstract

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.

Authors

Bennett O.V. Shum, Charles R. Mackay, Cem Z. Gorgun, Melinda J. Frost, Rakesh K. Kumar, Gökhan S. Hotamisligil, Michael S. Rolph

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Figure 3

Differential expression and regulation ofaP2 expression by PPARγ activation in HBEs and adipocytes.

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Differential expression and regulation ofaP2 ...
(A) HBEs and 3T3-L1 preadipocytes were treated with rosiglitazone (Ros.) or vehicle control and aP2 mRNA expression assessed. Data represent mean of 3 HBE and two 3T3-L1 experiments. (B) CD36 message levels were determined in HBEs after rosiglitazone treatment. Data represent mean of 2 experiments. (C) Relative abundance of aP2 message from 100 ng RNA was compared among human adipose tissue, HBEs, HBEs plus IL-4, THP-1 monocytes, and THP-1 monocytes plus PMA. (D) Transient transfection of BEAS-2B cells with WT STAT6, constitutively active STAT6 mutant (STAT6VT), or empty vector plasmids for 72 hours. aP2 expression was monitored by real-time PCR. Data represent mean ± SEM of 3 experiments. *P < 0.05 compared with vector control. (E) Transient transfection of BEAS-2B cells with STAT6 dominant negative (STAT6DN) or empty vector plasmids. Twenty-four hours after transfection, cells were treated with IL-4 for 18 hours, and aP2 transcript was quantified. Data represent mean ± SEM of 4 experiments. (F) Time course of aP2 expression in WT AECs after 3 or 18 hours treatment with IL-4 and TNF-α. Data represent the mean results from 2 independent cultures. (G) STAT6-deficient AECs were cultured in vitro and treated with IL-4 for 18 hours, and aP2 mRNA expression was assessed. Data represent the mean results of 2 independent cultures.