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. 1996 Dec;89(4):606–612. doi: 10.1046/j.1365-2567.1996.d01-780.x

MUTZ-3, a monocytic model cell line for interleukin-4 and lipopolysaccharide studies.

H Quentmeier 1, A Duschl 1, Z B Hu 1, B Schnarr 1, M Zaborski 1, H G Drexler 1
PMCID: PMC1456585  PMID: 9014829

Abstract

The human monocytic cell lines MUTZ-3 and MONO-MAC-6 express the lipopolysaccharide (LPS) receptor CD14. Paralleling the situation in peripheral blood monocytes (PBMo), recombinant human interleukin-4 (IL-4) down-regulated the expression of CD14 on the cell surface of MUTZ-3, but not that of MONO-MAC-6 cells. In addition, preincubation with IL-4 prevented the LPS-induced up-regulation of IL-1 beta mRNA levels in MUTZ-3, but not in MONO-MAC-6 cells. We examined whether the differential responsiveness of the cell lines was due to the missing expression of the IL-4 receptor (IL-4R) alpha or gamma c chain in MONO-MAC-6 cells. Flow cytometric and immunoprecipitation analysis revealed expression of both IL-4R chains in both cell lines. In addition, short-term stimulation with IL-4 induced tyrosine-phosphorylation of the gamma c chain. As both cell lines also expressed signal transducer and activator of transcription 6 (STAT 6), our data suggested that the differential reaction patterns of MUTZ-3 and MONO-MAC-6 cells were not due to a generally defective IL-4R complex. Interestingly, long-term (48 hr) treatment with LPS rendered MONO-MAC-6 cells sensitive to IL-4. LPS up-regulated expression of monocyte-specific esterase (MSE) mRNA as well as CD14 protein in MONO-MAC-6 cells; both effects were inhibited by IL-4. This stimulation was not paralleled by an increase of IL-4R mRNA or protein expression supporting the above hypothesis of a constitutively present and active IL-4R. We discuss possible causes for the differential reaction patterns of MUTZ-3 and MONO-MAC-6 cells to IL-4.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Dokter W. H., Esselink M. T., Halie M. R., Vellenga E. Interleukin-4 inhibits the lipopolysaccharide-induced expression of c-jun and c-fos messenger RNA and activator protein-1 binding activity in human monocytes. Blood. 1993 Jan 15;81(2):337–343. [PubMed] [Google Scholar]
  2. Donnelly R. P., Crofford L. J., Freeman S. L., Buras J., Remmers E., Wilder R. L., Fenton M. J. Tissue-specific regulation of IL-6 production by IL-4. Differential effects of IL-4 on nuclear factor-kappa B activity in monocytes and fibroblasts. J Immunol. 1993 Nov 15;151(10):5603–5612. [PubMed] [Google Scholar]
  3. Essner R., Rhoades K., McBride W. H., Morton D. L., Economou J. S. IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. J Immunol. 1989 Jun 1;142(11):3857–3861. [PubMed] [Google Scholar]
  4. Hou J., Schindler U., Henzel W. J., Ho T. C., Brasseur M., McKnight S. L. An interleukin-4-induced transcription factor: IL-4 Stat. Science. 1994 Sep 16;265(5179):1701–1706. doi: 10.1126/science.8085155. [DOI] [PubMed] [Google Scholar]
  5. Hu Z. B., Ma W., Zaborski M., MacLeod R., Quentmeier H., Drexler H. G. Establishment and characterization of two novel cytokine-responsive acute myeloid and monocytic leukemia cell lines, MUTZ-2 and MUTZ-3. Leukemia. 1996 Jun;10(6):1025–1040. [PubMed] [Google Scholar]
  6. Ihle J. N., Witthuhn B. A., Quelle F. W., Yamamoto K., Silvennoinen O. Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol. 1995;13:369–398. doi: 10.1146/annurev.iy.13.040195.002101. [DOI] [PubMed] [Google Scholar]
  7. Jansen J. H., Fibbe W. E., Wientjens G. J., Van Damme J., Landegent J. E., Willemze R., Kluin-Nelemans J. C. Interleukin 4 down-regulates the expression of CD14 and the production of interleukin 6 in acute myeloid leukemia cells. Lymphokine Cytokine Res. 1991 Dec;10(6):457–461. [PubMed] [Google Scholar]
  8. Landmann R., Ludwig C., Obrist R., Obrecht J. P. Effect of cytokines and lipopolysaccharide on CD14 antigen expression in human monocytes and macrophages. J Cell Biochem. 1991 Dec;47(4):317–329. doi: 10.1002/jcb.240470406. [DOI] [PubMed] [Google Scholar]
  9. Landmann R., Zimmerli W., Sansano S., Link S., Hahn A., Glauser M. P., Calandra T. Increased circulating soluble CD14 is associated with high mortality in gram-negative septic shock. J Infect Dis. 1995 Mar;171(3):639–644. doi: 10.1093/infdis/171.3.639. [DOI] [PubMed] [Google Scholar]
  10. Lauener R. P., Goyert S. M., Geha R. S., Vercelli D. Interleukin 4 down-regulates the expression of CD14 in normal human monocytes. Eur J Immunol. 1990 Nov;20(11):2375–2381. doi: 10.1002/eji.1830201103. [DOI] [PubMed] [Google Scholar]
  11. Musso T., Johnston J. A., Linnekin D., Varesio L., Rowe T. K., O'Shea J. J., McVicar D. W. Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7. J Exp Med. 1995 Apr 1;181(4):1425–1431. doi: 10.1084/jem.181.4.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ruppert J., Friedrichs D., Xu H., Peters J. H. IL-4 decreases the expression of the monocyte differentiation marker CD14, paralleled by an increasing accessory potency. Immunobiology. 1991 Aug;182(5):449–464. doi: 10.1016/S0171-2985(11)80209-3. [DOI] [PubMed] [Google Scholar]
  13. Wang L. M., Keegan A., Frankel M., Paul W. E., Pierce J. H. Signal transduction through the IL-4 and insulin receptor families. Stem Cells. 1995 Jul;13(4):360–368. doi: 10.1002/stem.5530130407. [DOI] [PubMed] [Google Scholar]
  14. Wang L. M., Myers M. G., Jr, Sun X. J., Aaronson S. A., White M., Pierce J. H. IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells. Science. 1993 Sep 17;261(5128):1591–1594. doi: 10.1126/science.8372354. [DOI] [PubMed] [Google Scholar]
  15. te Velde A. A., Huijbens R. J., Heije K., de Vries J. E., Figdor C. G. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood. 1990 Oct 1;76(7):1392–1397. [PubMed] [Google Scholar]

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