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Gene Review

Lta  -  lymphotoxin alpha

Rattus norvegicus

Synonyms: LT-alpha, Lymphotoxin-alpha, TNF-beta, Tnfb, Tnfsf1, ...
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Disease relevance of Lta

  • We now report that TNF beta and TNF alpha (1-100 ng/ml) can protect cultured embryonic rat hippocampal, septal, and cortical neurons against glucose deprivation-induced injury and excitatory amino acid toxicity [1].
  • Tumor necrosis factors (TNF alpha and TNF beta), cytokines that are expressed in response to brain injury, induced the expression of calbindin in cultured rat hippocampal and neocortical astrocytes [2].
  • The growth of C6 glioma cells was stimulated by TNF-alpha, IFN-gamma and IL-6 but not by TNF-beta [3].
  • The expression of TGFbeta1, TGFbeta2, TGFbeta3, TNFalpha, TNFbeta and lymphotoxin beta (Ltbeta) was significantly higher in adenocarcinomas than in normal lung tissues [4].

High impact information on Lta

  • The elevation of intracellular calcium concentration ([Ca2+]i) induced by glucose deprivation, glutamate, NMDA, or AMPA was attenuated in neurons pretreated with TNF beta [1].
  • IL-1 beta, IL-12 and TNF-beta mRNA expression in brain tissue sections appeared early and peaked at the height of clinical signs in both acute and PR-EAE, consistent with a disease-promoting role for these cytokines [5].
  • Our analyses have shown that while IL-1alpha, IL-1beta, TNF-alpha, TNF-beta, and TGF-beta1 transcripts are abundantly expressed by cultured microglia, they are very low to virtually undetectable in the SVCC [6].
  • Manganese superoxide dismutase induced by TNF-beta is regulated transcriptionally by NF-kappaB after spinal cord injury in rats [7].
  • We have isolated an approximately 22-kb TNF locus (encoding tumor necrosis factor) from a rat genomic library and sequenced the 7105-bp fragment that comprises the TNF-alpha and TNF-beta genes, including their flanking sequences [8].

Biological context of Lta

  • The mechanism whereby TNFs stabilize [Ca2+]i may involve regulation of the expression of proteins involved in maintaining [Ca2+]i homeostasis, since both TNF beta and TNF alpha caused a 4- to 8-fold increase in the number of neurons expressing the calcium-binding protein calbindin-D28k [1].
  • Induction of TNF alpha and TNF beta gene expression in rat cardiac transplants during allograft rejection [9].
  • The two genes are tandemly arranged with TNF-beta 5' to TNF-alpha and separated by approximately 1.1 kb of intergenic space, and each gene consists of four exons and three introns, similar to those of the other species examined thus far [8].

Anatomical context of Lta


Associations of Lta with chemical compounds

  • The aim of the present study was to determine the effects of low-dose CsA/MTX on the expression of the cytotoxic cytokines, TNF alpha, TNF beta, or lymphotoxin (LT), and the serine proteases HF and C11 (granzymes A and B, respectively) in rat cardiac allografts during rejection [15].
  • The effect of tumor necrosis factor-alpha (TNF alpha) and tumor necrosis factor-beta (TNF beta) on the capsaicin-induced increase in cutaneous blood flow was investigated in anaesthetized rats [16].

Other interactions of Lta

  • TNF alpha was also a good stimulator of lymphocyte migration, while TNF beta and IL-1 alpha were weak or nearly inactive [17].
  • In contrast, the brain of S. pneumoniae-inoculated rats showed lower levels of IL-1beta, IL-6 and TNF-alpha, but higher levels of TNF-beta and detectable mRNA expression of IL-4 when compared with Hib-inoculated rats [18].
  • However, neither the pretreatment with TNF alpha (5-5000 pg) nor that with TNF beta (50-5000 pg) enhanced the vasodilatator response to intraplantar capsaicin (0.03 micrograms; 0.1 microgram), whereas 50 pg interleukin-1 beta augmented the capsaicin-induced hyperaemia (P < 0.05) [16].

Analytical, diagnostic and therapeutic context of Lta


  1. Tumor necrosis factors protect neurons against metabolic-excitotoxic insults and promote maintenance of calcium homeostasis. Cheng, B., Christakos, S., Mattson, M.P. Neuron (1994) [Pubmed]
  2. Brain injury and tumor necrosis factors induce calbindin D-28k in astrocytes: evidence for a cytoprotective response. Mattson, M.P., Cheng, B., Baldwin, S.A., Smith-Swintosky, V.L., Keller, J., Geddes, J.W., Scheff, S.W., Christakos, S. J. Neurosci. Res. (1995) [Pubmed]
  3. Involvement of nitric oxide on the cytokine induced growth of glial cell. Muñoz-Fernández, M.A., Fresno, M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  4. Elevated expression of transforming growth factor betas and the tumor necrosis factor family in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. Tsujiuchi, T., Sasaki, Y., Murata, N., Tsutsumi, M., Nakae, D., Konishi, Y. Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie. (2001) [Pubmed]
  5. High IL-6 and low IL-10 in the central nervous system are associated with protracted relapsing EAE in DA rats. Diab, A., Zhu, J., Xiao, B.G., Mustafa, M., Link, H. J. Neuropathol. Exp. Neurol. (1997) [Pubmed]
  6. Cytokine transcripts expressed by microglia in vitro are not expressed by ameboid microglia of the developing rat central nervous system. Hurley, S.D., Walter, S.A., Semple-Rowland, S.L., Streit, W.J. Glia (1999) [Pubmed]
  7. Manganese superoxide dismutase induced by TNF-beta is regulated transcriptionally by NF-kappaB after spinal cord injury in rats. Yune, T.Y., Lee, S.M., Kim, S.J., Park, H.K., Oh, Y.J., Kim, Y.C., Markelonis, G.J., Oh, T.H. J. Neurotrauma (2004) [Pubmed]
  8. Cloning and sequence analysis of the rat tumor necrosis factor-encoding genes. Kwon, J., Chung, I.Y., Benveniste, E.N. Gene (1993) [Pubmed]
  9. Induction of TNF alpha and TNF beta gene expression in rat cardiac transplants during allograft rejection. Pizarro, T.T., Malinowska, K., Kovacs, E.J., Clancy, J., Robinson, J.A., Piccinini, L.A. Transplantation (1993) [Pubmed]
  10. In situ localization of TNFalpha/beta, TACE and TNF receptors TNF-R1 and TNF-R2 in control and LPS-treated lung tissue. Ermert, M., Pantazis, C., Duncker, H.R., Grimminger, F., Seeger, W., Ermert, L. Cytokine (2003) [Pubmed]
  11. Effects of six different cytokines on lymphocyte adherence to microvascular endothelium and in vivo lymphocyte migration in the rat. Issekutz, T.B. J. Immunol. (1990) [Pubmed]
  12. Activation of C-jun N-terminal kinase/stress-activated protein kinase in primary glial cultures. Zhang, P., Miller, B.S., Rosenzweig, S.A., Bhat, N.R. J. Neurosci. Res. (1996) [Pubmed]
  13. Modulation of intrathecal morphine-induced immunosuppression by microinjection of naloxone into periaqueductal gray. Zhang, Y., Du, L.N., Wu, G.C., Cao, X.D. Zhongguo yao li xue bao = Acta pharmacologica Sinica. (1998) [Pubmed]
  14. Dentin sialoprotein and phosphoprotein induce neutrophil recruitment: a mechanism dependent on IL-1beta, TNF-beta, and CXC chemokines. Silva, T.A., Lara, V.S., Silva, J.S., Garlet, G.P., Butler, W.T., Cunha, F.Q. Calcif. Tissue Int. (2004) [Pubmed]
  15. Diminished cytotoxic gene expression in rat cardiac transplants with low-dose cyclosporine/methotrexate combination therapy. Pizarro, T.T., Malinowska, K., Kovacs, E.J., Clancy, J., Robinson, J.A., Piccinini, L.A. Transplantation (1994) [Pubmed]
  16. Tumor necrosis factor-alpha prevents interleukin-1 beta from augmenting capsaicin-induced vasodilatation in the rat skin. Herbert, M.K., Hering, S. Eur. J. Pharmacol. (1995) [Pubmed]
  17. Stimulation of lymphocyte migration by endotoxin, tumor necrosis factor, and interferon. Issekutz, T.B., Stoltz, J.M. Cell. Immunol. (1989) [Pubmed]
  18. Haemophilus influenzae and Streptococcus pneumoniae induce different intracerebral mRNA cytokine patterns during the course of experimental bacterial meningitis. Diab, A., Zhu, J., Lindquist, L., Wretlind, B., Bakhiet, M., Link, H. Clin. Exp. Immunol. (1997) [Pubmed]
  19. Effect of SLS-2 spaceflight on immunologic parameters of rats. Lesnyak, A., Sonnenfeld, G., Avery, L., Konstantinova, I., Rykova, M., Meshkov, D., Orlova, T. J. Appl. Physiol. (1996) [Pubmed]
  20. Effects of NF-kappaB oligonucleotide "decoys" on gene expression in P7 rat hippocampus after hypoxia/ischemia. Qiu, J., Hu, X., Nesic, O., Grafe, M.R., Rassin, D.K., Wood, T.G., Perez-Polo, J.R. J. Neurosci. Res. (2004) [Pubmed]
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