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Effects of interferons beta or gamma on neopterin biosynthesis and tryptophan degradation by human alveolar macrophages in vitro: synergy with lipopolysaccharide.
Am J Respir Cell Mol Biol. 1992 Jun; 6(6):639-46.AJ

Abstract

Interferons can induce neopterin biosynthesis and tryptophan degradation in monocytic cells. Indoleamine 2,3-dioxygenase (IDO), an inducible cellular enzyme, metabolizes tryptophan to N-formyl-L-kynurenine. Tryptophan degradation has been linked to interferon-mediated inhibition of replication by intracellular pathogens and inhibition of cancer cell proliferation. We evaluated the ability of the recombinant human interferons beta ser and gamma to stimulate neopterin production and tryptophan degradation in vitro by alveolar macrophages (AM) obtained from normal volunteers by bronchoalveolar lavage. Additionally, because other biologic response modifiers such as lipopolysaccharide (LPS) can also stimulate monocytic cells to produce increased amounts of neopterin and degrade tryptophan, we evaluated the effects of LPS on interferon-induced neopterin production and tryptophan degradation by AM. Both interferon-gamma (IFN-gamma) and interferon-beta (IFN-beta) induced neopterin production and tryptophan degradation by AM with corresponding inhibition of intracellular replication by Chlamydia psittaci in AM, but IFN-gamma was a more potent inducer of these responses than IFN-beta. LPS enhanced neopterin production and tryptophan degradation by interferon-exposed cells. This effect was particularly evident at lower concentrations of interferon, and LPS synergy was more pronounced with IFN-beta than IFN-gamma. Concentrations of LPS that alone had no stimulatory effect on tryptophan degradation synergistically enhanced the induction of IDO activity by lower concentrations of interferon. These studies suggest that IFN-gamma stimulates human AM to produce neopterin and degrade tryptophan more potently than IFN-beta, and that low concentrations of LPS can synergistically enhance such effects of interferons on tissue macrophage metabolism.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Medicine, University of Wisconsin, Madison.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

1591013

Citation

Meyer, K C., et al. "Effects of Interferons Beta or Gamma On Neopterin Biosynthesis and Tryptophan Degradation By Human Alveolar Macrophages in Vitro: Synergy With Lipopolysaccharide." American Journal of Respiratory Cell and Molecular Biology, vol. 6, no. 6, 1992, pp. 639-46.
Meyer KC, Cornwell R, Carlin JM, et al. Effects of interferons beta or gamma on neopterin biosynthesis and tryptophan degradation by human alveolar macrophages in vitro: synergy with lipopolysaccharide. Am J Respir Cell Mol Biol. 1992;6(6):639-46.
Meyer, K. C., Cornwell, R., Carlin, J. M., Powers, C., Irizarry, A., Byrne, G. I., & Borden, E. C. (1992). Effects of interferons beta or gamma on neopterin biosynthesis and tryptophan degradation by human alveolar macrophages in vitro: synergy with lipopolysaccharide. American Journal of Respiratory Cell and Molecular Biology, 6(6), 639-46.
Meyer KC, et al. Effects of Interferons Beta or Gamma On Neopterin Biosynthesis and Tryptophan Degradation By Human Alveolar Macrophages in Vitro: Synergy With Lipopolysaccharide. Am J Respir Cell Mol Biol. 1992;6(6):639-46. PubMed PMID: 1591013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of interferons beta or gamma on neopterin biosynthesis and tryptophan degradation by human alveolar macrophages in vitro: synergy with lipopolysaccharide. AU - Meyer,K C, AU - Cornwell,R, AU - Carlin,J M, AU - Powers,C, AU - Irizarry,A, AU - Byrne,G I, AU - Borden,E C, PY - 1992/6/1/pubmed PY - 1992/6/1/medline PY - 1992/6/1/entrez SP - 639 EP - 46 JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. VL - 6 IS - 6 N2 - Interferons can induce neopterin biosynthesis and tryptophan degradation in monocytic cells. Indoleamine 2,3-dioxygenase (IDO), an inducible cellular enzyme, metabolizes tryptophan to N-formyl-L-kynurenine. Tryptophan degradation has been linked to interferon-mediated inhibition of replication by intracellular pathogens and inhibition of cancer cell proliferation. We evaluated the ability of the recombinant human interferons beta ser and gamma to stimulate neopterin production and tryptophan degradation in vitro by alveolar macrophages (AM) obtained from normal volunteers by bronchoalveolar lavage. Additionally, because other biologic response modifiers such as lipopolysaccharide (LPS) can also stimulate monocytic cells to produce increased amounts of neopterin and degrade tryptophan, we evaluated the effects of LPS on interferon-induced neopterin production and tryptophan degradation by AM. Both interferon-gamma (IFN-gamma) and interferon-beta (IFN-beta) induced neopterin production and tryptophan degradation by AM with corresponding inhibition of intracellular replication by Chlamydia psittaci in AM, but IFN-gamma was a more potent inducer of these responses than IFN-beta. LPS enhanced neopterin production and tryptophan degradation by interferon-exposed cells. This effect was particularly evident at lower concentrations of interferon, and LPS synergy was more pronounced with IFN-beta than IFN-gamma. Concentrations of LPS that alone had no stimulatory effect on tryptophan degradation synergistically enhanced the induction of IDO activity by lower concentrations of interferon. These studies suggest that IFN-gamma stimulates human AM to produce neopterin and degrade tryptophan more potently than IFN-beta, and that low concentrations of LPS can synergistically enhance such effects of interferons on tissue macrophage metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/1591013/Effects_of_interferons_beta_or_gamma_on_neopterin_biosynthesis_and_tryptophan_degradation_by_human_alveolar_macrophages_in_vitro:_synergy_with_lipopolysaccharide_ L2 - http://www.atsjournals.org/doi/full/10.1165/ajrcmb/6.6.639?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -