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Figure 2 | Arthritis Research & Therapy

Figure 2

From: Glucocorticoids: do we know how they work?

Figure 2

Glucocorticoids may act (1) by transcriptional interference and (2) by inhibiting MAP kinases. The left side represents glucocorticoid (G) combining with its receptor (GR) and inducing gene expression by binding to DNA glucocorticoid response elements (GREs). The right side shows an inflammatory stimulus (e.g. lipopolysaccharide, IL-1, tumour necrosis factor) activating protein kinase cascades (see Fig. 3) and inducing inflammatory response genes. (1) Transcriptional interference is due to the liganded GR directly binding the transcription factors activator protein-1 and nuclear factor-κB and inhibiting their action. (2) Glucocorticoid-induced genes, possibly MAP kinase phosphatases, inhibit MAP kinase signalling pathways by keeping them in the dephosphorylated state. This would inhibit both transcriptional and post-transcriptional mechanisms underlying inflammatory gene expression. MAP = mitogen-activated protein.

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