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BMC Immunology

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01-12-2021 | Glucocorticoid | Research article

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

Authors: Wen-Teng Chang, Ming-Yuan Hong, Chien-Liang Chen, Chi-Yuan Hwang, Cheng-Chieh Tsai, Chia-Chang Chuang

Published in: BMC Immunology | Issue 1/2021

Abstract

Background

Glucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines, such as interleukin (IL)-6.

Results

Five putative GR binding sites and other transcriptional factor binding sites were identified on theIL-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, nuclear factor-kappa B (NF-κB), activator protein (AP)-1, and specificity protein (Sp)1–2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The second GR binding site (GR2) was noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation.

Conclusions

We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.

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Title: Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects
Authors: Wen-Teng Chang
Ming-Yuan Hong
Chien-Liang Chen
Chi-Yuan Hwang
Cheng-Chieh Tsai
Chia-Chang Chuang
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Glucocorticoid
Dexamethasone
Published in: BMC Immunology / Issue 1/2021
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/s12865-021-00413-z

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