| Autor: |
Li, Zhouya, Davis, Gerald S., Mohr, Carsten, Nain, Marianne, Gemsa, Diethard |
| Zdroj: |
Immunobiology; October 1996, Vol. 195 Issue: 4-5 p640-654, 15p |
| Abstrakt: |
Microtubule disrupting agents such as colchicine have been shown to reduce TNF-α production in macrophages. To examine molecular mechanisms underlying the action of colchicine, TNF-α gene expression was studied in the murine macrophage cell line PU5-1.8. An LPS stimulation caused an intense up-regulation of TNF-α gene expression which was followed by a high TNF-α protein production. Simultaneous addition of colchicine (10 μM) suppressed LPS-induced TNF-α mRNA accumulation by one-third and TNF-α protein release by two-thirds. This effect was shared by vinblastine and vincristine, chemically different agents that also disrupt microtubule polymerization. For full suppressive activity on TNF-α gene expression, colchicine had to be present for 3 h in LPS-stimulated macrophage cultures. With nuclear run-on transcription experiments we could demonstrate that colchicine primarily inhibited de novogene transcription and did not accelerate degradation of TNF-α mRNA in actinomycin D-treated macrophages. Thus, the wellknown antiinflammatory action of microtubule depolymerizing agents may be largely due to a reduced TNF-α gene expression. |
| Databáze: |
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