Hypoxia inducible factor 1 alpha (HIF-1alpha) induces corticosteroid-insensitive inflammation via reduction of histone deacetylase-2 (HDAC2) transcription. Export

@article{citeulike:6071689, abstract = {Corticosteroids are potent anti-inflammatory agents, but corticosteroid insensitivity is a major barrier for the treatment of some chronic inflammatory diseases. Here we show that hypoxia induces corticosteroid-insensitive inflammation via reduced transcription of histone deacetylase-2 (HDAC2) in lung epithelial and macrophage cells. HDAC2 mRNA and protein expression were reduced under hypoxic conditions (1\% O2). Hypoxia enhanced IL-1beta-induced interleukin-8 (CXCL-8) production in A549 cells and decreased the ability of dexamethasone to suppress the CXCL-8 production. Deletion or point mutation studies revealed that binding of the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) to a HIF response element (HRE) at -320, but not HIF-1beta or HIF-2alpha, results in reduced Polymerase II (Pol II) binding at the site leading to reduced promoter activity of HDAC2. Our results suggest that activation of HIF-1alpha by hypoxia decreases HDAC2 levels, resulting in amplified inflammation and corticosteroid resistance.}, author = {Charron, Catherine E. and Chou, Pai-Chien C. and Coutts, David J. and Kumar, Vaibhav and To, Masako and Akashi, Kenichi and Pinhu, Liao and Griffiths, Mark and Adcock, Ian M. and Barnes, Peter J. and Ito, Kazuhiro}, citeulike-article-id = {6071689}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M109.025387}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19880520}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19880520}, day = {30}, doi = {10.1074/jbc.M109.025387}, issn = {1083-351X}, journal = {The Journal of biological chemistry}, keywords = {1, alpha, corticosteroid-insensitive, deacetylase-2, factor, hdac2, hif-1alpha, histone, hypoxia, induces, inducible, inflammation, of, reduction, transcription, via}, month = {October}, posted-at = {2009-11-04 22:29:26}, priority = {2}, title = {Hypoxia inducible factor 1 alpha (HIF-1{alpha}) induces corticosteroid-insensitive inflammation via reduction of histone deacetylase-2 (HDAC2) transcription.}, url = {http://dx.doi.org/10.1074/jbc.M109.025387}, year = {2009} }

TY - JOUR ID - citeulike:6071689 L3 - citeulike-article-id:6071689 N2 - Corticosteroids are potent anti-inflammatory agents, but corticosteroid insensitivity is a major barrier for the treatment of some chronic inflammatory diseases. Here we show that hypoxia induces corticosteroid-insensitive inflammation via reduced transcription of histone deacetylase-2 (HDAC2) in lung epithelial and macrophage cells. HDAC2 mRNA and protein expression were reduced under hypoxic conditions (1% O2). Hypoxia enhanced IL-1beta-induced interleukin-8 (CXCL-8) production in A549 cells and decreased the ability of dexamethasone to suppress the CXCL-8 production. Deletion or point mutation studies revealed that binding of the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) to a HIF response element (HRE) at -320, but not HIF-1beta or HIF-2alpha, results in reduced Polymerase II (Pol II) binding at the site leading to reduced promoter activity of HDAC2. Our results suggest that activation of HIF-1alpha by hypoxia decreases HDAC2 levels, resulting in amplified inflammation and corticosteroid resistance. JF - The Journal of biological chemistry SN - 1083-351X TI - Hypoxia inducible factor 1 alpha (HIF-1{alpha}) induces corticosteroid-insensitive inflammation via reduction of histone deacetylase-2 (HDAC2) transcription. KW - 1 KW - alpha KW - corticosteroid-insensitive KW - deacetylase-2 KW - factor KW - hdac2 KW - hif-1alpha KW - histone KW - hypoxia KW - induces KW - inducible KW - inflammation KW - of KW - reduction KW - transcription KW - via AU - Charron, Catherine AU - Chou, Pai-Chien AU - Coutts, David AU - Kumar, Vaibhav AU - To, Masako AU - Akashi, Kenichi AU - Pinhu, Liao AU - Griffiths, Mark AU - Adcock, Ian AU - Barnes, Peter AU - Ito, Kazuhiro PY - 2009/10/30/ UR - http://dx.doi.org/10.1074/jbc.M109.025387 ER -