| First Author | Kalinichenko VV | Year | 1999 |
| Journal | J Immunol | Volume | 163 |
| Issue | 5 | Pages | 2492-9 |
| PubMed ID | 10452985 | Mgi Jnum | J:57098 |
| Mgi Id | MGI:1343677 | Doi | 10.4049/jimmunol.163.5.2492 |
| Citation | Kalinichenko VV, et al. (1999) Norepinephrine-mediated inhibition of antitumor cytotoxic T lymphocyte generation involves a beta-adrenergic receptor mechanism and decreased TNF-alpha gene expression. J Immunol 163(5):2492-9 |
| abstractText | 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-alpha 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-alpha production. Here, we show that NE inhibits the production of TNF-alpha 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-alpha revealed substantial NE-mediated decreases in the percentages of TNF-alpha+ cells among CD4+ and CD8+ T cells and F4/80+ activated macrophages. NE inhibition of CTL generation was largely overcome by addition of TNF-alpha to the stimulation cultures. When the beta-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-alpha 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-alpha synthesis through a mechanism(s) involving beta-adrenergic receptor signaling. |
