The Journal of Immunology, Vol 147, Issue 8 2603-2608, Copyright © 1991 by American Association of Immunologists

ARTICLES

Cytokine-induced IL-1 beta gene expression in the human polymorphonuclear leukocyte: transcriptional and post-transcriptional regulation by tumor necrosis factor and IL-1

PT Marucha, RA Zeff and DL Kreutzer
Department of Periodontology, Ohio State University College of Dentistry, Columbus 43210.

We have previously demonstrated that Il-1 and TNF could rapidly, but transiently, induce gene expression of Il-1 beta in human polymorphonuclear leukocytes (PMN) at both the protein and mRNA level. Additionally, we demonstrated a cooperative effect of Il-1 and TNF on the kinetics of induction of Il-1 beta mRNA and protein. In order to better understand the molecular basis of Il-1 beta induction, we have further investigated the regulation of Il-1 and TNF-induced gene expression in the PMN. Using nuclear run-on transcription analysis, we found that within 1 h Il-1, TNF, and TNF plus Il-1 induced the transcription of the Il-1 beta gene by 33-, 61-, and 99-fold, respectively. By 2 h, the levels of transcription had been reduced to approximately 50% of peak levels for TNF- and TNF plus Il-1-treated PMN, and to near noninduced levels in Il-1-treated PMN. We also found that these cytokines induced stable mRNA, i.e., Il-1 beta mRNA t1/2 for Il-1-, TNF-, and TNF plus Il-1-induced PMN were 57, 94, and 86 min, respectively. By 2 h, when steady state levels of Il-1 beta mRNA were found to decrease, Il-1 beta mRNA t1/2 had fallen to approximately 18 min for all cytokine treatments. To determine if protein synthesis was required for induction of Il-1 beta gene expression, we treated PMN simultaneously with cytokines and cycloheximide, and found that cycloheximide enhanced the accumulation of Il-1-induced Il-1 beta mRNA, but abrogated the accumulation of Il-1 beta mRNA, by TNF- or TNF plus Il-1-treated PMN. This abrogation of Il-1 beta mRNA accumulation was not caused by inhibition of induction of Il-1 beta transcription because TNF induction of transcription of Il-1 beta was not affected by simultaneous treatment with cycloheximide. Thus, we report that Il-1 and TNF regulate IL-1 beta gene expression via both transcriptional and post-transcriptional mechanisms in vitro.

This article has been cited by other articles:

				A. Cloutier, T. Ear, E. Blais-Charron, C. M. Dubois, and P. P. McDonald Differential involvement of NF-{kappa}B and MAP kinase pathways in the generation of inflammatory cytokines by human neutrophils J. Leukoc. Biol., February 1, 2007; 81(2): 567 - 577. [Abstract] [Full Text] [PDF]

				P. S. D. Weber, S. A. Madsen-Bouterse, G. J. M. Rosa, S. Sipkovsky, X. Ren, P. E. Almeida, R. Kruska, R. G. Halgren, J. L. Barrick, and J. L. Burton Analysis of the bovine neutrophil transcriptome during glucocorticoid treatment Physiol Genomics, December 13, 2006; 28(1): 97 - 112. [Abstract] [Full Text] [PDF]

				P. Rice, E. Martin, J.-R. He, M. Frank, L. DeTolla, L. Hester, T. O'Neill, C. Manka, I. Benjamin, A. Nagarsekar, et al. Febrile-Range Hyperthermia Augments Neutrophil Accumulation and Enhances Lung Injury in Experimental Gram-Negative Bacterial Pneumonia J. Immunol., March 15, 2005; 174(6): 3676 - 3685. [Abstract] [Full Text] [PDF]

				A. Cloutier, T. Ear, O. Borissevitch, P. Larivee, and P. P. McDonald Inflammatory Cytokine Expression Is Independent of the c-Jun N-Terminal Kinase/AP-1 Signaling Cascade in Human Neutrophils J. Immunol., October 1, 2003; 171(7): 3751 - 3761. [Abstract] [Full Text] [PDF]

				C. N Serhan and C. B Clish Aspirin triggered lipid mediators: novel inhibitors of leucocyte trafficking Thorax, October 1, 2000; 55(90002): 10S - 12. [Full Text]

				M. Hachicha, M. Pouliot, N. A. Petasis, and C. N. Serhan Lipoxin (LX)A4 and Aspirin-triggered 15-epi-LXA4 Inhibit Tumor Necrosis Factor 1alpha -initiated Neutrophil Responses and Trafficking: Regulators of a Cytokine-Chemokine Axis J. Exp. Med., June 21, 1999; 189(12): 1923 - 1930. [Abstract] [Full Text] [PDF]

				P. P. McDonald, A. Bald, and M. A. Cassatella Activation of the NF-kappa B Pathway by Inflammatory Stimuli in Human Neutrophils Blood, May 1, 1997; 89(9): 3421 - 3433. [Abstract] [Full Text] [PDF]

				S. A. Schreyer, J. J. Peschon, and R. C. LeBoeuf Accelerated Atherosclerosis in Mice Lacking Tumor Necrosis Factor Receptor p55 J. Biol. Chem., October 18, 1996; 271(42): 26174 - 26178. [Abstract] [Full Text] [PDF]

				A. R. Lloyd, A. Biragyn, J. A. Johnston, D. D. Taub, L. Xu, D. Michiel, H. Sprenger, J. J. Oppenheim, and D. J. Kelvin Granulocyte-Colony Stimulating Factor and Lipopolysaccharide Regulate the Expression of Interleukin 8 Receptors on Polymorphonuclear Leukocytes J. Biol. Chem., November 24, 1995; 270(47): 28188 - 28192. [Abstract] [Full Text] [PDF]