| First Author | Reddy J | Year | 2001 |
| Journal | Int Immunol | Volume | 13 |
| Issue | 2 | Pages | 135-47 |
| PubMed ID | 11157847 | Mgi Jnum | J:67178 |
| Mgi Id | MGI:1930017 | Doi | 10.1093/intimm/13.2.135 |
| Citation | Reddy J, et al. (2001) IL-2-induced tumor necrosis factor (TNF)-ss expression: further analysis in the IL-2 knockout model, and comparison with TNF-alpha, lymphotoxin-ss, TNFR1 and TNFR2 modulation. Int Immunol 13(2):135-47 |
| abstractText | IL-2 induces the stimulation of inflammatory and immune reactions, and the apoptosis of antigen-activated cells. However, the molecular basis of these pleiotropic functions is largely unknown. We have previously reported that IL-2 induces genes involved in cytoskeleton organization, oncogene regulation and transcriptional control. In an IL-2-dependent cell line, we have also shown that IL-2 induces tumor necrosis factor (TNF)-ss mRNA through the Jak-STAT pathway. Here, we first demonstrate in vitro that IL-2 induces mature and partially spliced TNF-ss mRNA in the splenocytes and lymph node cells of both IL-2(-/-) and IL-2(+/-) mice. Under the same experimental conditions, IL-2 is seen to induce TNF-alpha mRNA. mRNA expression is followed by semiquantitative RT-PCR and this analysis is then extended in vivo by studying different lymphoid organs from IL-2(-/-)animals. Strikingly, the expression of TNF-ss mRNA is noted to be extremely low in the spleens and lymph nodes of IL-2(-/-) mice. Similarly, TNF-alpha, lymphotoxin (LT)-ss, TNFR1 and TNFR2 mRNA levels are also low in the spleens of IL-2(-/-) animals, whereas IFN-gamma and IL-4 mRNA levels remain unaffected in these animals. The experimental values are significantly different (P: </= 0.05) from those of control IL-2(+/-) animals. Western blot analysis of TNF-alpha expression confirmed and extended the results at the protein level. For the first time, we demonstrate that IL-2 directly or indirectly regulates genes of the TNF-TNFR family in secondary lymphoid organs. Furthermore, IL-2(-/-) animals in which thymopoiesis is unaffected show normal expression of these genes. Altogether, our data further define the pleiotropic effects of IL-2 at the molecular level. |
