Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function.
Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function.
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DOI：
10.1007/s00109-012-0986-9
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发表时间：
2013-05
影响因子：
4.7
通讯作者：
Nizet, Victor
中科院分区：
文献类型：
--
作者：
Alexander, Laura E. Crotty;Akong-Moore, Kathryn;Feldstein, Stephanie;Johansson, Per;Anh Nguyen;McEachern, Elisa K.;Nicatia, Shari;Cowburn, Andrew S.;Olson, Joshua;Cho, Jae Youn;Isaacs, Hart, Jr.;Johnson, Randall S.;Broide, David H.;Nizet, Victor
关键词：
Hypoxia-inducible factor (HIF)-1α is a master regulator of inflammatory activities of myeloid cells, including neutrophils and macrophages. These studies examine the role of myeloid cell HIF-1α in regulating asthma induction and pathogenesis, and for the first time, evaluate the roles of HIF-1α and HIF-2α in the chemotactic properties of eosinophils, the myeloid cells most associated with asthma. Wild-type (WT) and myeloid cell-specific HIF-1α knockout (KO) C57BL/6 mice were studied in an ovalbumin (OVA) model of asthma. Administration of the pharmacological HIF-1α antagonist YC-1 was used to corroborate findings from the genetic model. WT, HIF-1α, and HIF-2α KO eosinophils underwent in vitro chemotaxis assays. We found that deletion of HIF-1α in myeloid cells and systemic treatment with YC-1 during asthma induction decreased airway hyperresponsiveness (AHR). Deletion of HIF-1α in myeloid cells in OVA-induced asthma also reduced eosinophil infiltration, goblet cell hyperplasia, and levels 34 of cytokines IL-4, IL-5, and IL-13 in the lung. HIF-1α inhibition with YC-1 during asthma induction decreased eosinophilia in bronchoalveolar lavage, lung parenchyma, and blood, as well as decreased total lung inflammation, IL-5, and serum OVA-specific IgE levels. Deletion of HIF-1α in eosinophils decreased their chemotaxis, while deletion of the isoform HIF-2α led to increased chemotaxis. This work demonstrates that HIF-1α in myeloid cells plays a role in asthma pathogenesis, particularly in AHR development. Additionally, treatment with HIF-1α inhibitors during asthma induction decreases AHR and eosinophilia. Finally, we show that HIF- 1α and HIF-2α regulate eosinophil migration in opposing ways.
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影响因子：
8.7
作者：
Bhakta NR;Woodruff PG
通讯作者：
Woodruff PG
影响因子：
8.6
作者：
Huerta-Yepez, S.;Baay-Guzman, G. J.;Bonavida, B.
通讯作者：
Bonavida, B.
影响因子：
5.4
作者：
Kim, So Ri;Lee, Kyung Sun;Lee, Yong Chul
通讯作者：
Lee, Yong Chul
DOI：
10.1152/ajplung.00219.2005
发表时间：
2006-05-01
影响因子：
4.9
作者：
Careau, É;Proulx, LI;Bissonnette, ÉY
通讯作者：
Bissonnette, ÉY
影响因子：
14.2
作者：
Bochner, Bruce S.;Hamid, Qutayba
通讯作者：
Hamid, Qutayba