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bioRxiv · 10.1101/2020.06.24.168666

Mutant glucocorticoid receptor binding elements on Interleukin-6 promoter regulate dexamethasone effects

Chang, W.-T.·Hong, M.-Y.·Chen, C.-L.·Tsai, C.-C.·Hwang, C.-Y.·Chuang, C.-C.
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Abstract

Glucocorticoid has been widely used as an important modulator for clinical infectious and inflammatory disease. Glucocorticoid receptor (GR) is a transcription factor belonging to the family of nuclear receptors, regulated anti-inflammatory process and the release of pro-inflammatory cytokines. Five putative GR and other transcription factor binding sites on interleukin (IL)-6 promoter were identified and dexamethasone could reduce LPS-induced IL-6 release. Among them, the mutant transcriptional factors NF-{kappa}B, AP-1, and Sp1-2 site decreased the basal and effects of lipopolysaccharide (LPS)-induced IL-6 promoter activities in different responses. GR2/3 seemed to be an important role in both basal and inducible promoter activities in LPS-induced inflammation. We concluded that the selective GR2/3 modulators may have agonistic and antagonistic combined effects and activate important signaling pathway during LPS-stimulated inflammatory process.

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Chang, W.-T., Hong, M.-Y., Chen, C.-L., Tsai, C.-C., Hwang, C.-Y., Chuang, C.-C.. 2020-06-24. Mutant glucocorticoid receptor binding elements on Interleukin-6 promoter regulate dexamethasone effects. https://doi.org/10.1101/2020.06.24.168666

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