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Updated: Jul 19, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Modification of glucocorticoid sensitivity by MAP kinase signaling pathways in glucocorticoid-induced T-cell
Tomoko Tanaka1, Taijiro Okabe, Shigeki Gondo
1Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Objective:
Glucocorticoid is widely used for the treatment of diseases such as hematological malignancies. Glucocorticoid sensitivity is different from person to person and the mechanism of the regulation of glucocorticoid sensitivity is not well known. Glucocorticoid resistance is a major clinical problem.
Methods And Results:
Here, using glucocorticoid-induced T-cell apoptosis, a model system for the analysis of the mechanism of glucocorticoid action, we clarified that mitogen-activated protein kinases (MAPKs) modify glucocorticoid sensitivity, namely that the activation of extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase reduce and enhance glucocorticoid sensitivity, respectively.
Conclusion:
These findings might provide new tools for overcoming glucocorticoid-resistance.
Insights
Mitogen-activated protein kinases (MAPKs) influence glucocorticoid sensitivity. Understanding how extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase affect sensitivity may help overcome glucocorticoid resistance in patients.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- Glucocorticoids are essential therapeutics for hematological malignancies.
- Individual variability in glucocorticoid sensitivity and resistance presents a significant clinical challenge.
- The precise mechanisms regulating glucocorticoid sensitivity remain incompletely understood.
Purpose of the Study:
- To investigate the role of mitogen-activated protein kinases (MAPKs) in modulating glucocorticoid sensitivity.
- To elucidate how specific MAPKs impact glucocorticoid-induced T-cell apoptosis.
Main Methods:
- Utilized glucocorticoid-induced T-cell apoptosis as a model system.
- Analyzed the effects of MAPK activation on glucocorticoid sensitivity.
Main Results:
- Demonstrated that MAPKs significantly modify glucocorticoid sensitivity.
- Found that extracellular signal-regulated protein kinase (ERK) activation decreases glucocorticoid sensitivity.
- Showed that p38 MAP kinase activation enhances glucocorticoid sensitivity.
Conclusions:
- These findings offer novel insights into the regulation of glucocorticoid sensitivity.
- The identified MAPK pathways represent potential targets for overcoming glucocorticoid resistance.
- This research may lead to improved therapeutic strategies for glucocorticoid-resistant conditions.
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