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Distinct roles of the two tumor necrosis factor (TNF) receptors in modulating TNF and lymphotoxin alpha effects.
J Biol Chem. 1996 Apr 19; 271(16):9778-84.JB

Abstract

The role for the two tumor necrosis factor (TNF) receptors in discriminating TNF and lymphotoxin alpha (LTalpha) effects has been studied. TNF and LTalpha were equally mitogenic in Fs4 fibroblasts, which express a high amount of the p55 compared to the p75 TNF receptors (TNFRs). In contrast, TNF was more potent than LTalpha in mediating gene regulation and cytotoxicity in SW480-betaGal cells and KYM-1 cells, which have a high p75/p55 TNFR ratio. Both TNF and LTalpha showed comparable affinities for the two TNFRs. However, in contrast to LTalpha, TNF dissociated rapidly from the p75 TNFR, whereas both cytokines dissociated slowly from the p55 TNFR. Soluble p55 TNFR was much more potent than soluble p75 TNFR in inhibiting TNF cytotoxicity, whereas both soluble receptors moderately decreased LTalpha-mediated cytotoxicity with comparable efficacy. Antagonistic monoclonal antibodies against either TNFR types markedly inhibited TNF effects. However, only the p55 TNFR antagonistic antibody significantly decreased LTalpha-mediated cytotoxicity and cytomegalovirus promoter activation, whereas blocking of the p75 TNFR enhanced the LTalpha effects. These data suggest that whereas the p75 TNFR can both directly propagate TNF signals and "pass" TNF to the p55 TNFR, it attenuates LTalpha and may serve as a decoy receptor for this cytokine.

Authors+Show Affiliations

Institute of Cancer Research and Molecular Biology, Trondheim, Norway.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8621658

Citation

Medvedev, A E., et al. "Distinct Roles of the Two Tumor Necrosis Factor (TNF) Receptors in Modulating TNF and Lymphotoxin Alpha Effects." The Journal of Biological Chemistry, vol. 271, no. 16, 1996, pp. 9778-84.
Medvedev AE, Espevik T, Ranges G, et al. Distinct roles of the two tumor necrosis factor (TNF) receptors in modulating TNF and lymphotoxin alpha effects. J Biol Chem. 1996;271(16):9778-84.
Medvedev, A. E., Espevik, T., Ranges, G., & Sundan, A. (1996). Distinct roles of the two tumor necrosis factor (TNF) receptors in modulating TNF and lymphotoxin alpha effects. The Journal of Biological Chemistry, 271(16), 9778-84.
Medvedev AE, et al. Distinct Roles of the Two Tumor Necrosis Factor (TNF) Receptors in Modulating TNF and Lymphotoxin Alpha Effects. J Biol Chem. 1996 Apr 19;271(16):9778-84. PubMed PMID: 8621658.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct roles of the two tumor necrosis factor (TNF) receptors in modulating TNF and lymphotoxin alpha effects. AU - Medvedev,A E, AU - Espevik,T, AU - Ranges,G, AU - Sundan,A, PY - 1996/4/19/pubmed PY - 1996/4/19/medline PY - 1996/4/19/entrez SP - 9778 EP - 84 JF - The Journal of biological chemistry JO - J Biol Chem VL - 271 IS - 16 N2 - The role for the two tumor necrosis factor (TNF) receptors in discriminating TNF and lymphotoxin alpha (LTalpha) effects has been studied. TNF and LTalpha were equally mitogenic in Fs4 fibroblasts, which express a high amount of the p55 compared to the p75 TNF receptors (TNFRs). In contrast, TNF was more potent than LTalpha in mediating gene regulation and cytotoxicity in SW480-betaGal cells and KYM-1 cells, which have a high p75/p55 TNFR ratio. Both TNF and LTalpha showed comparable affinities for the two TNFRs. However, in contrast to LTalpha, TNF dissociated rapidly from the p75 TNFR, whereas both cytokines dissociated slowly from the p55 TNFR. Soluble p55 TNFR was much more potent than soluble p75 TNFR in inhibiting TNF cytotoxicity, whereas both soluble receptors moderately decreased LTalpha-mediated cytotoxicity with comparable efficacy. Antagonistic monoclonal antibodies against either TNFR types markedly inhibited TNF effects. However, only the p55 TNFR antagonistic antibody significantly decreased LTalpha-mediated cytotoxicity and cytomegalovirus promoter activation, whereas blocking of the p75 TNFR enhanced the LTalpha effects. These data suggest that whereas the p75 TNFR can both directly propagate TNF signals and "pass" TNF to the p55 TNFR, it attenuates LTalpha and may serve as a decoy receptor for this cytokine. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/8621658/Distinct_roles_of_the_two_tumor_necrosis_factor__TNF__receptors_in_modulating_TNF_and_lymphotoxin_alpha_effects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(17)31402-3 DB - PRIME DP - Unbound Medicine ER -