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IL‐20 is regulated by hypoxia‐inducible factor and upregulated after experimental ischemic stroke
Author(s) -
CHEN WEI YU,
CHANG MING SHI
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb327
Subject(s) - downregulation and upregulation , hypoxia (environmental) , in vivo , medicine , in vitro , ischemia , brain ischemia , receptor , cancer research , pathology , immunology , biology , chemistry , gene , biochemistry , organic chemistry , oxygen , microbiology and biotechnology
IL‐20, an IL‐10 family member, is involved in various inflammatory diseases, such as psoriasis, rheumatoid arthritis, and atherosclerosis. We investigated whether hypoxia in vitro and an in vivo model of ischemic stroke would upregulate IL‐20 expression. In vitro, IL‐20 expression increased in hypoxic HaCaT , HEK293 cells, chondrocytes, monocytes and glioblastoma cells. Inhibiting HIF‐1alpha inhibited CoCl2‐induced IL‐20 expression. We identified two putative hypoxia response elements in human il20‐gene promoter. Promoter activity assays showed that CoCl2‐mimicked hypoxia activated luciferase reporter‐gene expression. In vivo, experimental ischemic stroke upregulated IL‐20 in the sera and brain tissue of rats. IL‐20 stained positively in glia‐like cells in peri‐infarcted lesions, but not in contralateral tissue. Administration of IL‐20 monoclonal antibody ameliorated ischemia‐induced brain infarction of rats after experimental ischemic stroke. In vitro, RT‐PCR analysis showed that glioblastoma cells GBM8901 cells expressed IL‐20 and its receptor subunits IL‐20R1, IL‐20R2, and IL‐22R1. IL‐20 also induced production of IL‐1beta, IL‐8, and MCP‐1 in GBM8901 cells. We conclude that IL‐20 was responsive to hypoxia in vitro and in the ischemic stroke model, and that upregulation of IL‐20 in the ischemic brain may contribute to brain injury.