Skip to main content
SpringerLink
Log in

Interferon-γ and lipopolysaccharide induce mouse guanylate-binding protein 3 (mGBP3) expression in the murine macrophage cell line RAW264.7

  • Research Articles
  • Microbiology & Immunology
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Mouse guanylate-binding protein 3 (mGBP3) is a 71-kDa GTPase which belongs to GTP-binding protein family. The present study showed that the expression of mGBP3 transcript was readily induced in a dose dependent fashion in the macrophage cell line RAW264.7 treated with either interferon-γ (IFN-γ) or lipopolysaccharide (LPS). The expression of mGBP3 protein was also apparent by 4 and 6 h after the treatment of cells with IFN-γ (100 U/ml) or LPS (1 μg/ml), and remained at plateau for at least 24 h. Cycloheximide (10 μg/ml) had no effect on the IFN-γ- or LPS-induced mGBP3 expression, suggesting that the mGBP3 induction did not require further protein synthesis. Interestingly, a protein kinase C (PKC) inhibitor staurosporine (50 nM) abolished the induction of mGBP3 expression by LPS, but not by IFN-γ. These findings suggest that mGBP3 may be involved in the macrophage activation process and both IFN-γ and LPS induce the mGBP3 expression through distinct signal transduction pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References Cited

  • Adams, D. O. and Hamilton, T. A. The cell biology of macrophage activation.Annu. Rev. Immunol. 2, 283–318 (1994).

    Article  Google Scholar 

  • Asundi, V. K., Stahl, R. C., Showalter, L., Conner, K. J. and Carey, D. J., Molecular cloning and characterization of an isoprenylated 67 kDa protein.Biochim. Biophys. Act. 1217, 257–265 (1994).

    CAS  Google Scholar 

  • Barber, S. A., Perera, P.-Y., McNally, R., and Vogel, S. N., The serine/threonine phosphatase inhibitor, calyculin A, inhibits and dissociates macrophage responses to lipopolysaccharide.J. Immunol. 155, 1404–1410 (1995).

    PubMed  CAS  Google Scholar 

  • Bourne, H. R., Sanders, D. A. and McCormick, F., The GTPase superfamily: conserved structure and molecular mechanism.Nature 349, 117–127 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Briken, V., Ruffner, H., Schultz, U., Schwarz, A., Reis, L. F., Strehlow, I., Deker, T. and Staeheli, P. Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma interferon.Mol. Cell Biol. 15, 975–982 (1995).

    PubMed  CAS  Google Scholar 

  • Cheng, Y-S. E., Patterson, C. E. and Staeheli, P. Interferon-induced guanylate-binding proteins lack an N(T)KXD consensus motif and bind GMP in addition to GDP and GTP.Mol. Cell. Biol. 11, 4717–4725 (1991).

    PubMed  CAS  Google Scholar 

  • Clarke, S., Protein isoprenylation and methylation at carboxyl terminal cysteine residues.Annu. Rev. Biochem. 61, 355–386 (1992).

    PubMed  CAS  Google Scholar 

  • Darnell, J. E., Jr., Kerr, I. M., and Stark, G. R., JAK-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.Science 264, 1415–1421 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Dickey, B. F. and Birnbaumer, L. (Eds) GTPase in Biology, Springer, Berlin, 1991.

    Google Scholar 

  • Dong, Z., Qi, X., Xie, K. and Fidler, I. J., Protein tyrosine kinase inhibitors decrease induction of nitric oxide synthase activity in lipopolysaccharide-responsive and lipopolysaccharide-nonresponsive murine macrophages.J. Immunol. 151, 2717–2724 (1993).

    PubMed  CAS  Google Scholar 

  • Fidler, I. J. Macrophages and metastasis- a biological approach to cancer therapy.Cancer Res. 45, 4714–4726 (1985).

    PubMed  CAS  Google Scholar 

  • Fidler, I. J. and Schroit, A. J. Recognition and destruction of neoplastic cells by activated macrophages: discrimination of altered self.Biochim Biophys. Acta 948, 151–173 (1988).

    PubMed  CAS  Google Scholar 

  • Foster, G. R. Interferons in host defence.Semin. Liver Dis. 17, 287–295 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Fujihara, M., Connolly, N., Ito, N. and Suzuki, T. Properties of protein kinase isoforms (beta II, epsilon, and zeta) in a macrophage cell line (J774) and their roles in LPS-induced nitric oxide production.J. Immunol. 152, 1898–1906 (1994).

    PubMed  CAS  Google Scholar 

  • Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S. and Tannenbaum, S. R., Anaylsis of nitrate, nitrite, and [15N]nitrate in biological fluids.Anal. Biochem. 126, 131–138 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Han, B. H., Park, D. J., Lim, R. W., Im, J. H., and Kim, H. D., Cloning, expression, and characterization of a novel guanylate-binding protein3, mGBP3 in the murine erythroid progenitor cells.Biochim. Biophys. Act. 1384, 373–386 (1998).

    CAS  Google Scholar 

  • Harada, H., Takahashi, E.-I., Itoh, S., Harada, K., Hori, T.-A. and Taniguchi, T. Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system.Mol. Cell. Biol. 14, 1500–1509 (1994).

    PubMed  CAS  Google Scholar 

  • Jun, C.-D., Choi, B.-M., Ryu, H., Um, J.-Y., Kwak, H.-J., Lee, B.-S., Paik, S.-G., Kim, H.-M. and Chung, H.-T. Synergistic cooperation between phorbol esters and IFN-γ for induction of nitric oxide synthesis in murine peritioneal macrophages.J. Immunol. 153, 3684–3690 (1994).

    PubMed  CAS  Google Scholar 

  • Manavalan, P., Dearborn, D. G., McPherson, J. M. and Smith, A. E. Sequence homologies between nucleotide binding regions of CFTR and G-proteins suggest structural and functional similarities.FEBS Lett. 366, 87–91 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Marshall, C. J., Protein prenylation: a mediator of protein-protein interactions.Science 259, 1865–1866 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Meßmer, U. K., Reed, J. C. and Brune, B. Bcl-2 protects macrophages from nitric oxide-induced apoptosis.J. Biol. Chem. 271, 20192–20197 (1996).

    Article  PubMed  Google Scholar 

  • Neun, R., Richter, M. F., Staeheli, P. and Schwemmle, M., GTPase properties of the interferon-induced human guanylate-binding protein 2.FEBS Lett. 390, 69–72 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Nicolet, C. M. and Paulock, D. M. Promoter analysis of an interferon-inducible gene associated with macrophage activation.J. Immunol. 152, 153–162 (1994).

    PubMed  CAS  Google Scholar 

  • Nonaka, K., Ishisaki, A., Muro, M., Kato, S., Oido, M., Nakashima, K., Kowashi, Y. and Nishihara, T., Possible involvement of protein kinase C in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans.FEMS Microbiol. Lett. 159, 247–254 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Novogrodsky, A., Vanichkin, A., Patya, M., Gazit, A., Osherov, N. and Levitzki, A., Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors.Science 264, 1319–1322 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Park, D. J., Lim, R. W. and Kim, H. D., Rapid induction of mouse virus-like (VL30) element transcripts by erythropoietin in murine progenitor cells.Blood 82, 77–83 (1993).

    PubMed  CAS  Google Scholar 

  • Reimann, T., Buscher, D., Hipskind, R. A., Krautwald, S., Lohmann-Matthes, M.-L. and Baccarini, M., Lipopolysaccharide induces activation of the Raf-1/MAP kinase pathway. A putative role for Raf-1 in the induction of the IL-1 beta and the TNF-alpha genes.J. Immunol. 153, 5740–5749 (1994).

    PubMed  CAS  Google Scholar 

  • Sands, W. A., Clark, J. S. and Liew, F. Y. The role of a phosphatidylcholine-specific phospholipase C in the production of diacylglycerol for nitric oxide synthesis in macrophages activated by IFN-gamma and LPS.Biochem. Biophys. Res. Commun. 199, 461–466 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Sano, H., Hirai, M., Saito, H., Nakashima, I., and Isobe, K.-I., A nitric oxide-releasing reagent, S-nitroso-N-acetylpenicillamine, enhances the expression of superoxide dismutases mRNA in the murine macrophage cell line RAW264.7.Immunol. 92, 118–122 (1997).

    Article  CAS  Google Scholar 

  • Schroeder, R. A., Delta Torre, A. and Kuo, P. C., CD 14-dependent mechanism for endotoxin-mediated nitric oxide synthesis in murine macrophages.Am. J. Physiol. 273, C1030-C1039 (1997).

    PubMed  CAS  Google Scholar 

  • Schwemmle, M. and Staeheli, P. The interferon-induced 67-kDa guanylate-binding protein (hGBP1) is a GTPase that converts GTP to GMP.J. Biol. Chem. 269, 11299–11305 (1994).

    PubMed  CAS  Google Scholar 

  • Schwemmle, M., Kaspers, B., Irion, A., Staeheli, P. and Schultz, U., Chicken guanylate-binding protein, conservation of GTPase activity and induction by cytokines.J. Biol. Chem. 271, 10304–10308 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Shuai, K., Schindler, C., Prezioso, V. R. and Darnell, J. E. Jr., Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein.Science 258, 1808–1812 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Sorace, J. M., Johnson, R. J., Howard, D. L. and Drysdale, B. E., Identification of an endotoxin and IFN-inducible cDNA: possible identification of a novel protein family.J Leukoc. Biol. 58, 477–484 (1995).

    PubMed  CAS  Google Scholar 

  • Strehlow, I., Lohmann-Matthes, M.-L. and Decker, T., The interferon-inducible GBP1 gene: structure and mapping to human chromosome 1.Gene 144, 295–299 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Vestal, D. J., Buss, J. E., Kelner, G. S., Maciejewski, D., Asundi, V. K. and Maki, R. A., Rat p67 GBP is induced by interferon-γ and isoprenoid-modified in macrophages.Biochem. Biophys. Res. Commun. 224, 528–534 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Wynn, T. A., Nicolet, C. M. and Paulnock, D. M. Identification and characterization of a new gene family induced during macrophage activation.J. Immunol. 147, 4384–4392 (1991).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, box 8111, 63110, St. Louis, MO, USA

    Byung Hee Han

Authors
  1. Byung Hee Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Han, B.H. Interferon-γ and lipopolysaccharide induce mouse guanylate-binding protein 3 (mGBP3) expression in the murine macrophage cell line RAW264.7. Arch Pharm Res 22, 130–136 (1999). https://doi.org/10.1007/BF02976536

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02976536

Key words

Search

Navigation