Abstract
Human monocytes, preincubated with IFN-γ respond to IL-4 by a cGMP increase through activation of an inducible NO synthase. Here, IL-4 was found to induce an accumulation of cGMP (1 – 3 min) and cAMP (20 – 25 min) in unstimulated monocytes. This was impaired with NOS inhibitors, but also with EGTA and calcium/calmodulin inhibitors. These results suggest that: (1) IL-4 may stimulate different NOS isoforms in resting and IFN-γ activated monocytes, and (2) cAMP accumulation may be partially dependent on the NO pathway. By RT-PCR, a type III constitutive NOS mRNA was detected in U937 monocytic cells. IL-4 also increased the [Ca2+]i in these cells. Different NOS may thus be expressed in monocytic cells depending on their differentiation and the signals they receive.
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- Arruda S., Ho J. L. IL-4 receptor signal transduction in human monocytes is associated with protein kinase C translocation. J Immunol. 1992 Aug 15;149(4):1258–1264. [PubMed] [Google Scholar]
- Aversa G., Punnonen J., Cocks B. G., de Waal Malefyt R., Vega F., Jr, Zurawski S. M., Zurawski G., de Vries J. E. An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13-induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for a common component shared by IL-4 and IL-13 receptors. J Exp Med. 1993 Dec 1;178(6):2213–2218. doi: 10.1084/jem.178.6.2213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bhaskaran G., Nii A., Sone S., Ogura T. Differential effects of interleukin-4 on superoxide anion production by human alveolar macrophages stimulated with lipopolysaccharide and interferon-gamma. J Leukoc Biol. 1992 Aug;52(2):218–223. doi: 10.1002/jlb.52.2.218. [DOI] [PubMed] [Google Scholar]
- Endres S., Fülle H. J., Sinha B., Stoll D., Dinarello C. A., Gerzer R., Weber P. C. Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells. Immunology. 1991 Jan;72(1):56–60. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Galizzi J. P., Zuber C. E., Harada N., Gorman D. M., Djossou O., Kastelein R., Banchereau J., Howard M., Miyajima A. Molecular cloning of a cDNA encoding the human interleukin 4 receptor. Int Immunol. 1990;2(7):669–675. doi: 10.1093/intimm/2.7.669. [DOI] [PubMed] [Google Scholar]
- Geller D. A., Lowenstein C. J., Shapiro R. A., Nussler A. K., Di Silvio M., Wang S. C., Nakayama D. K., Simmons R. L., Snyder S. H., Billiar T. R. Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3491–3495. doi: 10.1073/pnas.90.8.3491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ho J. L., Zhu B., He S., Du B., Rothman R. Interleukin 4 receptor signaling in human monocytes and U937 cells involves the activation of a phosphatidylcholine-specific phospholipase C: a comparison with chemotactic peptide, FMLP, phospholipase D, and sphingomyelinase. J Exp Med. 1994 Oct 1;180(4):1457–1469. doi: 10.1084/jem.180.4.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Idzerda R. L., March C. J., Mosley B., Lyman S. D., Vanden Bos T., Gimpel S. D., Din W. S., Grabstein K. H., Widmer M. B., Park L. S. Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily. J Exp Med. 1990 Mar 1;171(3):861–873. doi: 10.1084/jem.171.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keegan A. D., Nelms K., Wang L. M., Pierce J. H., Paul W. E. Interleukin 4 receptor: signaling mechanisms. Immunol Today. 1994 Sep;15(9):423–432. doi: 10.1016/0167-5699(94)90272-0. [DOI] [PubMed] [Google Scholar]
- Kolb J. P., Abadie A. Inhibitors of protein tyrosine kinases and protein tyrosine phosphatases suppress IL-4-induced CD23 expression and release by human B lymphocytes. Eur Cytokine Netw. 1993 Nov-Dec;4(6):429–438. [PubMed] [Google Scholar]
- Kolb J. P., Paul-Eugene N., Damais C., Yamaoka K., Drapier J. C., Dugas B. Interleukin-4 stimulates cGMP production by IFN-gamma-activated human monocytes. Involvement of the nitric oxide synthase pathway. J Biol Chem. 1994 Apr 1;269(13):9811–9816. [PubMed] [Google Scholar]
- Kondo M., Takeshita T., Ishii N., Nakamura M., Watanabe S., Arai K., Sugamura K. Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science. 1993 Dec 17;262(5141):1874–1877. doi: 10.1126/science.8266076. [DOI] [PubMed] [Google Scholar]
- Kotanides H., Reich N. C. Requirement of tyrosine phosphorylation for rapid activation of a DNA binding factor by IL-4. Science. 1993 Nov 19;262(5137):1265–1267. doi: 10.1126/science.7694370. [DOI] [PubMed] [Google Scholar]
- Lasfar A., Amirand C., Ballini J. P., Kolb J. P. Activation pathways triggered by interleukin-4 in the human plasmacytoma cell line RPMI-8226--differences with resting B lymphocytes. Eur Cytokine Netw. 1993 May-Jun;4(3):213–221. [PubMed] [Google Scholar]
- 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]
- Lowenstein C. J., Glatt C. S., Bredt D. S., Snyder S. H. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6711–6715. doi: 10.1073/pnas.89.15.6711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lyons C. R., Orloff G. J., Cunningham J. M. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. J Biol Chem. 1992 Mar 25;267(9):6370–6374. [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
- Musso T., Varesio L., Zhang X., Rowe T. K., Ferrara P., Ortaldo J. R., O'Shea J. J., McVicar D. W. IL-4 and IL-13 induce Lsk, a Csk-like tyrosine kinase, in human monocytes. J Exp Med. 1994 Dec 1;180(6):2383–2388. doi: 10.1084/jem.180.6.2383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
- Noguchi M., Nakamura Y., Russell S. M., Ziegler S. F., Tsang M., Cao X., Leonard W. J. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science. 1993 Dec 17;262(5141):1877–1880. doi: 10.1126/science.8266077. [DOI] [PubMed] [Google Scholar]
- Paul-Eugène N., Pène J., Bousquet J., Dugas B. Role of cyclic nucleotides and nitric oxide in blood mononuclear cell IgE production stimulated by IL-4. Cytokine. 1995 Jan;7(1):64–69. doi: 10.1006/cyto.1995.1008. [DOI] [PubMed] [Google Scholar]
- Paul W. E., Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. doi: 10.1146/annurev.iy.05.040187.002241. [DOI] [PubMed] [Google Scholar]
- Rasmussen H., Isales C., Ganesan S., Calle R., Zawalich W. Ca(2+)-cyclic AMP interactions in sustained cellular responses. Ciba Found Symp. 1992;164:98–112. [PubMed] [Google Scholar]
- Reiling N., Ulmer A. J., Duchrow M., Ernst M., Flad H. D., Hauschildt S. Nitric oxide synthase: mRNA expression of different isoforms in human monocytes/macrophages. Eur J Immunol. 1994 Aug;24(8):1941–1944. doi: 10.1002/eji.1830240836. [DOI] [PubMed] [Google Scholar]
- Rodriguez J., Quignard J. F., Fagni L., Lafon-Cazal M., Bockaert J. Blockade of nitric oxide synthesis by tyrosine kinase inhibitors in neurones. Neuropharmacology. 1994 Nov;33(11):1267–1274. doi: 10.1016/0028-3908(94)90026-4. [DOI] [PubMed] [Google Scholar]
- Russell S. M., Keegan A. D., Harada N., Nakamura Y., Noguchi M., Leland P., Friedmann M. C., Miyajima A., Puri R. K., Paul W. E. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science. 1993 Dec 17;262(5141):1880–1883. doi: 10.1126/science.8266078. [DOI] [PubMed] [Google Scholar]
- Schindler C., Kashleva H., Pernis A., Pine R., Rothman P. STF-IL-4: a novel IL-4-induced signal transducing factor. EMBO J. 1994 Mar 15;13(6):1350–1356. doi: 10.1002/j.1460-2075.1994.tb06388.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stuehr D. J., Griffith O. W. Mammalian nitric oxide synthases. Adv Enzymol Relat Areas Mol Biol. 1992;65:287–346. doi: 10.1002/9780470123119.ch8. [DOI] [PubMed] [Google Scholar]
- Takeshita T., Asao H., Ohtani K., Ishii N., Kumaki S., Tanaka N., Munakata H., Nakamura M., Sugamura K. Cloning of the gamma chain of the human IL-2 receptor. Science. 1992 Jul 17;257(5068):379–382. doi: 10.1126/science.1631559. [DOI] [PubMed] [Google Scholar]
- Vercelli D., Jabara H. H., Lee B. W., Woodland N., Geha R. S., Leung D. Y. Human recombinant interleukin 4 induces Fc epsilon R2/CD23 on normal human monocytes. J Exp Med. 1988 Apr 1;167(4):1406–1416. doi: 10.1084/jem.167.4.1406. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang L. M., Keegan A. D., Li W., Lienhard G. E., Pacini S., Gutkind J. S., Myers M. G., Jr, Sun X. J., White M. F., Aaronson S. A. Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4032–4036. doi: 10.1073/pnas.90.9.4032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang L. M., Keegan A. D., Paul W. E., Heidaran M. A., Gutkind J. S., Pierce J. H. IL-4 activates a distinct signal transduction cascade from IL-3 in factor-dependent myeloid cells. EMBO J. 1992 Dec;11(13):4899–4908. doi: 10.1002/j.1460-2075.1992.tb05596.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Watanabe S., Kondo M., Takatsu K., Sugamura K., Arai K. Involvement of the interleukin-2 receptor gamma subunit in interleukin-4-dependent activation of mouse hematopoietic cells and splenic B cells. Eur J Immunol. 1995 Jan;25(1):126–131. doi: 10.1002/eji.1830250122. [DOI] [PubMed] [Google Scholar]
- Wieser M., Bonifer R., Oster W., Lindemann A., Mertelsmann R., Herrmann F. Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes. Blood. 1989 Apr;73(5):1105–1108. [PubMed] [Google Scholar]
- Wong H. L., Welch G. R., Brandes M. E., Wahl S. M. IL-4 antagonizes induction of Fc gamma RIII (CD16) expression by transforming growth factor-beta on human monocytes. J Immunol. 1991 Sep 15;147(6):1843–1848. [PubMed] [Google Scholar]
- Xie Q. W., Cho H. J., Calaycay J., Mumford R. A., Swiderek K. M., Lee T. D., Ding A., Troso T., Nathan C. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science. 1992 Apr 10;256(5054):225–228. doi: 10.1126/science.1373522. [DOI] [PubMed] [Google Scholar]
- Zurawski S. M., Vega F., Jr, Huyghe B., Zurawski G. Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction. EMBO J. 1993 Jul;12(7):2663–2670. doi: 10.1002/j.1460-2075.1993.tb05927.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Wit H., Hendriks D. W., Halie M. R., Vellenga E. Interleukin-4 receptor regulation in human monocytic cells. Blood. 1994 Jul 15;84(2):608–615. [PubMed] [Google Scholar]
- 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]
- te Velde A. A., Huijbens R. J., de Vries J. E., Figdor C. G. IL-4 decreases Fc gamma R membrane expression and Fc gamma R-mediated cytotoxic activity of human monocytes. J Immunol. 1990 Apr 15;144(8):3046–3051. [PubMed] [Google Scholar]
- te Velde A. A., Klomp J. P., Yard B. A., de Vries J. E., Figdor C. G. Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4. J Immunol. 1988 Mar 1;140(5):1548–1554. [PubMed] [Google Scholar]
