Taxol and colchicine increase LPS-induced pro-IL-1 beta production, but do not increase IL-1 beta secretion. A role for microtubules in the regulation of IL-1 beta production.
IL-1 beta is a proinflammatory cytokine secreted chiefly by monocytes and macrophages. Currently, much of its mechanism of processing and secretion is poorly understood, but there is increasing evidence that the microtubule system may be involved. For example, it is known that taxol and colchicine, two drugs that affect microtubule structure and function, increase LPS-induced IL-1 beta release. However, it is not known whether these drugs affect the synthesis of the 31-kDa precursor (pro-IL-1 beta) or the processing and release of mature IL-1 beta. To test this, an assay was used that allowed for the temporal separation of IL-1 beta synthesis and release. The addition of taxol or colchicine to the secretory phase of the assay resulted in no significant change in IL-1 beta release. However, when these drugs were added to the stimulus for IL-1 beta production, there was a significant increase in both IL-1 beta release and total IL-1 beta production, as measured by ELISA. These findings indicate that taxol and colchicine increase LPS-induced IL-1 beta release by an increase in the production of the precursor molecule. Thus, it is unlikely that microtubules are involved in the IL-1 beta secretory machinery in any significant manner, but they do play a role in the regulation of pro-IL-1 beta production.
O'Brien
J M
JM
Department of Internal Medicine, Ohio State University, Columbus 43210, USA.
Wewers
M D
MD
Moore
S A
SA
Allen
J N
JN
D000818:Animals; D002417:Cattle; D003078:Colchicine / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008870:Microtubules / Q000502:physiology*; D017239:Paclitaxel / Q000008:administration & dosage*; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012636:Secretory Rate / Q000187:drug effects
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011498:Protein Precursors; D017239:Paclitaxel; D003078:Colchicine