Affiliation:
1. *Center for Molecular Biology of Oral Diseases, and
2. †Department of Biochemistry and Molecular Biology, University of Illinois, Chicago, IL 60612
Abstract
Abstract
We have previously shown that norepinephrine (NE) inhibits the in vitro generation of anti-MOPC-315 CTL activity by spleen cells from BALB/c mice rejecting a large MOPC-315 tumor as a consequence of low-dose melphalan (l-phenylalanine mustard (l-PAM)) treatment (l-PAM TuB spleen cells). Since TNF-α plays a key role in the generation of antitumor CTL activity in this system, we determined whether NE mediates this inhibition through inhibition of TNF-α production. Here, we show that NE inhibits the production of TNF-α protein and mRNA by l-PAM TuB spleen cells stimulated in vitro with mitomycin C-treated tumor cells. Flow cytometric analysis of intracellular expression of TNF-α revealed substantial NE-mediated decreases in the percentages of TNF-α+ cells among CD4+ and CD8+ T cells and F4/80+ activated macrophages. NE inhibition of CTL generation was largely overcome by addition of TNF-α to the stimulation cultures. When the β-adrenergic antagonist propranolol was added to the stimulation cultures of l-PAM TuB spleen cells at a concentration that prevented NE-induced cAMP elevation, the NE-mediated decrease in TNF-α mRNA and NE-mediated inhibition of CTL generation were reversed. Collectively, these results suggest that NE inhibits antitumor CTL generation, at least in part, by inhibiting TNF-α synthesis through a mechanism(s) involving β-adrenergic receptor signaling.
Publisher
The American Association of Immunologists
Subject
Immunology,Immunology and Allergy
Reference28 articles.
1. Chambers, D. A., R. L. Cohen, R. L. Perlman. 1993. Neuroimmune modulation: signal transduction and catecholamines. Neurochem. Int. 22: 95
2. Felten, D. L., S. Y. Felten, S. L. Carlson, J. A. Olschowka, S. Livnat. 1985. Noradrenergic and peptidergic innervation of lymphoid tissue. J. Immunol. 135: 755
3. Felten, D. L., S. Y. Felten, D. L. Bellinger, S. L. Carlson, K. D. Ackerman, K. S. Madden, J. A. Olschowka, S. Livnat. 1987. Noradrenergic sympathetic neural interactions with the immune system: structure and function. Immunol. Rev. 100: 225
4. Madden, K. S., D. L. Felten. 1995. Experimental basis for neural-immune interactions. Physiol. Rev. 75: 77
5. Cook-Mills, J. M., R. L. Cohen, R. L. Perlman, D. A. Chambers. 1995. Inhibition of lymphocyte activation by catecholamines: evidence for a non-classical mechanism of catecholamine action. Immunology 85: 544
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