AJP - Lung Cellular and Molecular Physiology, Vol 261, Issue 4 315-L321, Copyright © 1991 by American Physiological Society

ARTICLES

Colchicine has opposite effects on interleukin-1 beta and tumor necrosis factor-alpha production

J. N. Allen, D. J. Herzyk and M. D. Wewers
Department of Internal Medicine, Ohio State University, Columbus 43210.

To study the role of microtubules in cytokine production, the effect of the microtubule depolymerizing agent colchicine on lipopolysaccharide endotoxin (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) release by blood monocytes and alveolar macrophages were examined. Immunofluorescence microscopy demonstrated that LPS resulted in the appearance of microtubule-containing cytoplasmic appendages and that colchicine, which resulted in microtubule disruption in monocytes, blocked appendage formation. Colchicine resulted in approximately 50% increase in LPS-induced IL-1 beta release and a 50% decrease in LPS-induced TNF-alpha release by human monocytes at all doses of LPS tested. Although colchicine resulted in a statistically significant increase in LPS-stimulated human alveolar macrophage IL-1 beta release, the increase was not as great as that observed with monocytes. Northern blot analysis suggested that the colchicine effect occurs pretranslationally because colchicine caused an increase in LPS-stimulated IL-1 beta mRNA levels and a decrease in TNF-alpha mRNA levels. These results suggest that microtubules contribute to the regulation of endotoxin-stimulated mononuclear phagocyte cytokine production and that this regulation differs significantly between IL-1 beta and TNF-alpha.

This article has been cited by other articles:

				N. Isowa, S. H. Keshavjee, and M. Liu Role of microtubules in LPS-induced macrophage inflammatory protein-2 production from rat pneumocytes Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1075 - L1082. [Abstract] [Full Text] [PDF]

				B. Cambien, M.-A. Millet, H. Schmid-Antomarchi, N. Brossette, B. Rossi, and A. Schmid-Alliana Src-Regulated Extracellular Signal-Related Kinase and Syk-Regulated c-Jun N-Terminal Kinase Pathways Act in Conjunction to Induce IL-1 Synthesis in Response to Microtubule Disruption in HL60 Cells J. Immunol., November 1, 1999; 163(9): 5079 - 5085. [Abstract] [Full Text] [PDF]

				N. Isowa, A. M. Xavier, E. Dziak, M. Opas, D. I. McRitchie, A. S. Slutsky, S. H. Keshavjee, and M. Liu LPS-induced depolymerization of cytoskeleton and its role in TNF-alpha production by rat pneumocytes Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L606 - L615. [Abstract] [Full Text] [PDF]

				A. Schmid-Alliana, L. Menou, S. Manie, H. Schmid-Antomarchi, M.-A. Millet, S. Giuriato, B. Ferrua, and B. Rossi Microtubule Integrity Regulates Src-like and Extracellular Signal-regulated Kinase Activities in Human Pro-monocytic Cells. IMPORTANCE FOR INTERLEUKIN-1 PRODUCTION J. Biol. Chem., February 6, 1998; 273(6): 3394 - 3400. [Abstract] [Full Text] [PDF]

				A. Rammes, J. Roth, M. Goebeler, M. Klempt, M. Hartmann, and C. Sorg Myeloid-related Protein (MRP) 8and MRP14, Calcium-binding Proteins of the S100 Family, Are Secreted by Activated Monocytes via a Novel, Tubulin-dependent Pathway J. Biol. Chem., April 4, 1997; 272(14): 9496 - 9502. [Abstract] [Full Text] [PDF]