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| DEXAMETHASONE INHIBITS THE INDUCTION OF MONOCYTE CHEMOTACTIC-ACTIVATING FACTOR PRODUCTION BY IL-1 OR TUMOR-NECROSIS-FACTOR |
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| Author(s): MUKAIDA N, ZACHARIAE CCO, GUSELLA GL, MATSUSHIMA K |
| Source: JOURNAL OF IMMUNOLOGY Volume: 146 Issue: 4 Pages: 1212-1215 Published: FEB 15 1991 |
| Times Cited: 106 References: 33 |
| Abstract: Recently purified and molecularly cloned monocyte chemotactic and activating factor (MCAF) may play a major role in recruiting and activating monocytes in the inflammatory process. We examined the effects of a potent anti-inflammatory agent, dexamethasone (DXS), on the production of this factor. Over a wide range of concentrations (10(-5) to 10(-8) M), DXS inhibited the production of MCAF at the mRNA and protein level in a human fibrosarcoma cell line, which was stimulated with either IL-1 or TNF-alpha. We examined the turn-over of synthesized MCAF mRNA that showed DXS decreased the stability of MCAF mRNA. Furthermore, the addition of actinomycin D and cycloheximide abolished this effect of DXS, indicating that de novo mRNA and protein synthesis were required for this process. In addition, a nuclear run-off analysis revealed that DXS also inhibited the transcription of IL-1- or TNF-activated MCAF genes. Therefore, both the destabilization of MCAF mRNA and the inhibition of transcription of the gene contribute to the decrease in the MCAF mRNA steady state level by DXS. |
| Document Type: Article |
| Language: English |
Addresses:
1. NCI, FREDERICK CANC RES & DEV CTR, DIV CANC TREATMENT, BIOL RESPONSE MODIFIERS PROGRAM, BLDG 560, FREDERICK, MD 21702 USA
2. NCI, FREDERICK CANC RES & DEV CTR, BIOCHEM PHYSIOL LAB, FREDERICK, MD 21702 USA
3. NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC, DYNCORP, FREDERICK, MD 21702 USA
4. NCI, FREDERICK CANC RES & DEV CTR, MOLEC IMMUNOREGULAT LAB, FREDERICK, MD 21702 USA |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Immunology |
| IDS Number: EW681 |
| ISSN: 0022-1767 |
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