Cell-specific regulation of apoptosis by glucocorticoids: implication to their anti-inflammatory action.
Glucocorticoids play a major role in attenuation of the inflammatory response. These steroid hormones are able to induce apoptosis in cells of the hematopoietic system such as monocytes, macrophages, and T lymphocytes that are involved in the inflammation reaction. In contrast, it was discovered recently that in glandular cells such as the mammary gland epithelia, hepatocytes, ovarian follicular cells, and in fibroblasts glucocorticoids protect against apoptotic signals evoked by cytokines, cAMP, tumor suppressors, and death genes. The anti-apoptotic effect of glucocorticoids is exerted by modulation of several survival genes such as Bcl-2, Bcl-x(L), and NFkB, in a cell-specific manner. Moreover, upregulation or downregulation of the same gene product can occur in a cell-dependent manner following stimulation by glucocorticoids. This phenomenon is probably due to composite regulatory cross-talk among multiple nuclear coactivators or corepressors, which mediate the transcription regulation of the genes, by their interaction with the glucocorticoid receptor. These observations suggest that the anti-inflammatory action of glucocorticoids is exerted by two complementary mechanisms: on one hand, they induce death of the cells that provoke the inflammation, and on the other hand they protect the resident cells of the inflamed tissue by arresting apoptotic signals. Moreover, the complementary action of glucocorticoids provides a new insight to the therapeutic potential of these hormones.
Amsterdam
Abraham
A
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. abraham.amsterdam@weizmann.ac.il
Tajima
Kimihisa
K
Sasson
Ravid
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D001940:Breast / Q000166:cytology / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D010053:Ovary / Q000166:cytology / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids