Molecular mechanisms of anti-inflammatory action of glucocorticoids.
Glucocorticoid hormones are effective in controlling inflammation, but the mechanisms that confer this action are largely unknown. Recent advances in this field have shown that both positive and negative regulation of gene expression are necessary for this process. The genes whose activity are modulated in the anti-inflammatory process code for several cytokines, adhesion molecules and enzymes. Most of them do not carry a classical binding site for regulation by a glucocorticoid receptor, but have instead regulatory sequences for transcription factors such as AP-1 or NF-kappa B. This makes them unusual targets for glucocorticoid action and emphasizes the need for novel regulatory mechanisms. Recent studies describe an important contribution by protein-protein interactions, in which several domains of the receptor participate; these studies provide a better understanding of the action of the receptor and offer opportunities for the design of steroidal compounds that could function more effectively as anti-inflammatory drugs.
Cato
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Forschungszentrum Karlsruhe, Institute of Genetics, Germany.
Wade
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D000818:Animals; D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004798:Enzymes / Q000096:biosynthesis; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004798:Enzymes; D005938:Glucocorticoids; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D014157:Transcription Factors