title: Hypoxia antagonizes glucose deprivation on interleukin 6 expression in an Akt dependent, but HIF-1/2α independent manner.
abstract: Although both glucose deprivation and hypoxia have been reported to promote cascades of biological alterations that lead to induction of inflammatory mediators, we hypothesized that glucose deprivation and hypoxia might show neutral, synergistic or antagonistic effects to each other on gene expression of inflammatory mediators depending on the regulatory components in their promoters. Gene expression of interleukin 6 (IL-6) was analyzed by real-time PCR, ELISA, or Western blot. Effects of glucose deprivation and/or hypoxia on activation of signaling pathways were analyzed by time-dependent phosphorylation patterns of signaling molecules. We demonstrate that hypoxia antagonized the effects of glucose deprivation on induction of IL-6 gene expression in microglia, macrophages, and monocytes. Hypoxia also antagonized thapsigargin-induced IL-6 gene expression. Hypoxia enhanced phosphorylation of Akt, and inhibition of Akt was able to reverse the effects of hypoxia on IL-6 gene expression. However, inhibition of HIF-1/2α did not reverse the effects of hypoxia on IL-6 gene expression. In addition, phosphorylation of p38, but not JNK, was responsible for the effects of glucose deprivation on IL-6 gene expression.
authors.affiliation: Laboratory of Genome to Drug Medicine, Joint Center for Biosciences, Incheon, Korea.
authors.forename: Sung Ji
authors.initials: SJ
authors.lastname: Choi
authors.forename: Ik Jae
authors.initials: IJ
authors.lastname: Shin
authors.forename: Kang-Hoon
authors.initials: KH
authors.lastname: Je
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Min
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hee-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Senyon
authors.initials: S
authors.lastname: Choe
authors.forename: Dong-Eog
authors.initials: DE
authors.lastname: Kim
authors.forename: Dong Kun
authors.initials: DK
authors.lastname: Lee
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005947:Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D048670:MAP Kinase Kinase 4; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D000099162:Endothelial PAS Domain-Containing Protein 1; C497443:Hif1a protein, mouse; C497444:Hif1a protein, rat