Skip to main content

Advertisement

Log in

Production of TNF-α, IL-1β, IL-12 and IFN-γ in murine peritoneal macrophages on treatment with wheat germ agglutinin in vitro: involvement of tyrosine kinase pathways

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Treatment of macrophages with various doses of wheat germ agglutinin (WGA) for different time intervals resulted in enhanced expression of TNF-α, IL-1β, IL-12 and IFN-γ. The maximum expressions were observed at 24 h with 100 ng/ml of WGA. Enhanced transcription of cytokines TNF-α, IL-1β, IL-12, and IFN-γ was observed at 16 h of WGA treatment by RT-PCR. Pharmacological inhibitor of tyrosine kinase, PI3 kinase, protein kinase C, p42/44, p38, JNK and intracellular calcium immobilizing agent down regulated the WGA induced expression of cytokines TNF-α, IL-1β, IL-12 and IFN-γ. Maximum protein tyrosine kinase activity in macrophages was seen at 5 min of WGA treatment. Maximum cytosolic Ca++ was observed at 10 min of WGA treatment. WGA treated macrophages showed maximum activation of protein kinase C (PKC) and PI3 kinase at 10 min, p42/44, p38 at 15 min and JNK at 30 min. Transcription factor ELK1 was activated at 60 min and IêB, c-Fos and c-Jun at 30 min of WGA treatment. The pharmacological inhibitors were also used to check the cascade of activation of tyrosine kinase, PKC, PI3 kinase, p42/44, p38, JNK and release of calcium from intracellular storage to sort out the signal pathways involved in the release of TNF-α, IL-1β, IL-12, and IFN-γ by macrophages on treatment with WGA in vitro.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Rosen, S.D., Bertozzi, C.R.: The selectins and their ligands. Curr. Opin. Cell. Biol. 6, 663–673 (1994)

    Article  PubMed  CAS  Google Scholar 

  2. Ofek, I., Sharon, N.: Lectinophagocytosis: a molecular mechanism of recognition between cell surface sugars and lectins in the phagocytosis of bacteria. Infect. Immun. 56, 539–547 (1988)

    PubMed  CAS  Google Scholar 

  3. Drysdale, B.E., Yapundich, R.A., Shin, M.L., Shin, H.S.: Lipopolysaccharide-mediated macrophage activation: the role of calcium in the generation of tumoricidal activity. J. Immunol. 138, 951–956 (1987)

    PubMed  CAS  Google Scholar 

  4. Oppenheim, J.J., Rosenstreich, D.L.: Signals regulating in vitro activation of lymphocytes. Prog. Allergy. 20, 65–194 (1976)

    Article  PubMed  CAS  Google Scholar 

  5. Perez, H.D., Elfman, F., Lobo, E.: Removal of human polymorphonuclear leukocyte surface sialic acid inhibits reexpression (or recycling) of formyl peptide receptors. A possible explanation for its effect on formyl peptide-induced polymorphonuclear leukocyte chemotaxis. J. Immunol. 139, 1978–1984 (1987)

    PubMed  CAS  Google Scholar 

  6. Sharon, N., Lis, H.: Lectins: cell-agglutinating and sugar-specific proteins. Science 177, 949–959 (1972)

    Article  PubMed  CAS  Google Scholar 

  7. Cohen, M.S., Metcalf, J.A., Root, R.K.: Regulation of oxygen metabolism in human granulocytes: relationship between stimulus binding and oxidative response using plant lectins as probes. Blood 55, 1003–1010 (1980)

    PubMed  CAS  Google Scholar 

  8. Hartshorn, K.L., Daigneault, D.E., White, M.R., Tauber, A.I.: Anomalous features of human neutrophil activation by influenza A virus are shared by related virus and sialic acid-binding lectins. J. Leukoc. Biol. 51, 230–236 (1992)

    PubMed  CAS  Google Scholar 

  9. Lock, R., Johansson, A., Orselius, K., Dahlgren, C.: Analysis of horseradish peroxidase amplified chemiluminescence produced by human neutrophils reveals a role for the superoxide anion in the light emitting reaction. Anal. Biochem. 173, 450–455 (1988)

    Article  PubMed  CAS  Google Scholar 

  10. Magnusson, K.E., Dahlgren, C., Sjolander, A.: Distinct pattern of granulocyte luminol-dependent chemiluminescence response to lectins WGA and RCA-1. Inflammation 12, 17–24 (1988)

    Article  PubMed  CAS  Google Scholar 

  11. Keisari, Y., Braun, L., Flescher, E.: The oxidative burst and related phenomena in mouse macrophages elicited by different sterile inflammatory stimuli. Immunobiology 165, 78–89 (1983)

    PubMed  CAS  Google Scholar 

  12. Tomioka, H., Saito, H.: Comparison of wheat germ agglutinin-and phorbol myristate acetate-mediated triggering for macrophage H2O2 release: susceptibilities to various macrophage inhibitors. Microbiol. Immunol. 31, 211–221 (1987)

    PubMed  CAS  Google Scholar 

  13. Karlsson, A.: Wheat germ agglutinin induces NADPH-oxidase activity in human neutrophils by interaction with mobilizable receptors. Infect. Immun. 67, 3461–3468 (1999)

    PubMed  CAS  Google Scholar 

  14. Stoika, R., Kashchak, N., Lutsik-Kordovsky, M., Boyko, M., Tsyrulnyk, A.: In vitro response of phagocytic cells to immunomodulating agents. Med. Sci. Monit. 7, 652–658 (2001)

    PubMed  CAS  Google Scholar 

  15. Chattopadhyay, U., Bhattacharyya, S.: Induction of tumor associated macrophage-mediated lysis of autologous tumor cells by lectins. Neoplasma 35, 321–328 (1988)

    PubMed  CAS  Google Scholar 

  16. Kesherwani, V., Sodhi, A.: Differential activation of macrophages in vitro by lectin Concanavalin, A., Phytohemagglutinin and Wheat germ agglutinin: Production and Regulation of Nitric oxide. Nitric Oxide 16, 294–305 (2007)

    Article  PubMed  CAS  Google Scholar 

  17. Adams, D.O., Nathan, C.F.: Molecular mechanisms in tumor-cell killing by activated macrophages. Immunol. Today 4, 166–170 (1983)

    Article  CAS  Google Scholar 

  18. Key, M.E., Hoyer, L., Bucana, C., Hanna, M.G. Jr.: Mechnaism of macrophage mediated tumor cytolysis. Adv. Exp. Med. Biol. 146, 265–310 (1982)

    PubMed  CAS  Google Scholar 

  19. Klostergaard, J., Leroux, M.E., Hung, M.C.: Cellular models of macrophage tumoricidal effector mechanism in vitro. Characterization of cytolytic response to tumor necrosis factor and nitric oxide pathways in vitro. J. Immunol. 147, 2802–2808 (1991)

    PubMed  CAS  Google Scholar 

  20. Sodhi, A., Singh, S.M.: Release of cytolytic factor(s) by murine macrophages in vitro on treatment with cis-platin. Int. J. Immunopharmacol. 8, 701–707 (1986)

    Article  PubMed  CAS  Google Scholar 

  21. Ranjan, P., Sodhi, A., Srivastava, A.: Cispaltin and interferon-gamma treated murine macrophage induce apoptosis in tumor cell lines. Anticancer Drugs 8, 1–10 (1997)

    Article  Google Scholar 

  22. Hibbs, J.B. Jr., Taintor, R.R., Vavrin, Z., Rachlin, E.M.: Nitric Oxide: a cytotoxic activated macrophage effector molecule. Biochem. Biophys. Res. Commun. 157, 87–94 (1988)

    Article  PubMed  CAS  Google Scholar 

  23. Joo, S.S., Chang, J.K., Park, J.H., Kang, H.C., Lee, D.I.: Immunoactivation of lectin-conjugated praecoxin A on IL-6, IL-12 expression. Arch. Pharm. Res. 25, 954–963 (2002)

    Article  PubMed  CAS  Google Scholar 

  24. Guan, J.L., Trevithick, J.E., Hynes, R.O.: Fibronectin/integrin interaction induces tyrosine phosphorylation of 120Kda proteins. Cell. Regul. 2, 951–964 (1991)

    PubMed  CAS  Google Scholar 

  25. Cooper, G.M.: The Cell a Molecular Approach, pp. 521–559. ASM, Washington, DC (2000)

    Google Scholar 

  26. Sodhi, A., Sethi, G.: Involvement of MAP kinase signal transduction pathway in UVB-induced activation of macrophages in vitro. Immunol. Lett. 90, 123–130 (2003)

    Article  PubMed  CAS  Google Scholar 

  27. Watowich, S.S., Wu, H., Socolovsky, M., Klingmuller, U., Constantinescu, S.N., Lodish, H.F.: Cytokine receptor signal transduction and the control of hematopoietic cell development. Annu. Rev. Cell. Dev. Biol. 12, 91–128 (1996)

    Article  PubMed  CAS  Google Scholar 

  28. Inazu, T., Taniguchi, T., Ohta, S., Miyabo, S., Yamamura, H.: The lectin wheat germ agglutinin induces rapid protein-tyrosine phosphorylation in human platelets. Biochem. Biophys. Res. Commun. 174, 1154–1158 (1991)

    Article  PubMed  CAS  Google Scholar 

  29. Ohmori, T., Yatomi, Y., Wu, Y., Osada, M., Satoh, K., Ozaki, Y.: Wheat germ agglutinin-induced platelet activation via platelet endothelial cell adhesion molecule-1: involvement of rapid phospholipase C gamma 2 activation by Src family kinases. Biochemistry 40, 12992–13001 (2001)

    Article  PubMed  CAS  Google Scholar 

  30. Sodhi, A., Singh, R.K., Singh, S.M.: Effect of interferon-gamma priming on the activation of murine peritoneal macrophages to the tumouricidal state by cisplatin, IL-1, and tumour necrosis factor (TNF): production of IL-1 and TNF. Clin. Exp. Immunol. 88, 350–355 (1992)

    Article  PubMed  CAS  Google Scholar 

  31. Sethi, G., Sodhi, A.: In vitro activation of murine peritoneal macrophages by ultraviolet B radiation: upregulation of CD18, production of NO, proinflammatory cytokines and a signal transduction pathway. Mol. Immunol. 40, 1315–1323 (2004)

    Article  PubMed  CAS  Google Scholar 

  32. Sodhi, A., Sethi, G.: Involvement of MAP kinase signal transduction pathway in UVB-induced activation of macrophages in vitro. Immunol. Lett. 90, 123–130 (2003)

    Article  PubMed  CAS  Google Scholar 

  33. Singh, R.A., Sodhi, A.: Cisplatin-treated macrophages produce oncostatin M: regulation by serine/threonine and protein tyrosine kinases/phosphatases and Ca2+/calmodulin. Immunol. Lett. 62, 159–164 (1998)

    Article  PubMed  CAS  Google Scholar 

  34. Mosmann, T.: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63 (1983)

    Article  PubMed  CAS  Google Scholar 

  35. Biswas, S.K., Sodhi, A.: In vitro activation of murine peritoneal macrophages by monocyte chemoattractant protein-1: upregulation of CD11b, production of proinflammatory cytokines, and the signal transduction pathway. J. Interferon. Cytokine. Res. 5, 527–538 (2002)

    Article  Google Scholar 

  36. Hamilton, T.A., Adams, D.O.: Molecular mechanisms of signal transduction in macrophages. Immunol. Today 8, 151–158 (1987)

    Article  CAS  Google Scholar 

  37. Weinstein, S.L., Gold, M.R., DeFranco, A.L.: Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages. Proc. Natl. Acad. Sci. U. S. A. 88, 4148–4152 (1991)

    Article  PubMed  CAS  Google Scholar 

  38. Kumar, R., Sodhi, A.: Activation of murine peritoneal macrophages with cisplatin and lipopolysaccharide: involvement of protein kinase C and tyrosine kinase. J. Clin. Biochem. Nutr. 17, 53–64 (1994)

    Google Scholar 

  39. Celada, A., Schreiber, R.D.: Role of protein kinase C and intracellular calcium mobilization in the induction of macrophages tumoricidal activity by Interferon-gamma. J. Immunol. 137, 2373–2379 (1986)

    PubMed  CAS  Google Scholar 

  40. Nakane, M., Mitchell, J., Förstermann, U., Murad, F.: Phosphorylation by calcium calmodulin-dependent protein kinase II and protein kinase C modulates the activity of nitric oxide synthase. Biochem. Biophys. Res. Commun. 180, 1396–1402 (1991)

    Article  PubMed  CAS  Google Scholar 

  41. Eason, S., Martin, W.: Involvement of tyrosine kinase and protein kinase C in the induction of nitric oxide synthase by lipopolysaccharids and interferon-gamma in J774 macrophages. Arch. Int. Pharmacodyn. 330, 225–236 (1995)

    PubMed  CAS  Google Scholar 

  42. Friedman, B., Frackelton, A.R. Jr., Ross, A.H., Connors, J.M., Fujiki, H., Sugimura, T., Rosner, M.R.: Tumor promoters block tyrosine-specific phosphorylation of the epidermal growth factor receptor. Proc. Natl. Acad. Sci. U. S. A. 81, 3034–3038 (1984)

    Article  PubMed  CAS  Google Scholar 

  43. Foulkes, J.G., Chow, M., Gorka, C., Frackelton, A.R. Jr., Baltimore, D.: Purification and characterization of a protein-tyrosine kinase encoded by the Abelson murine leukemia virus. J. Biol. Chem. 260, 8070–8077 (1985)

    PubMed  CAS  Google Scholar 

  44. Daniel, T.O., Tremble, P.M., Frackelton, A.R. Jr., Williams, L.T.: Purification of the platelet-derived growth factor receptor by using an anti-phosphotyrosine antibody. Proc. Natl. Acad. Sci. U. S. A. 82, 2684–2687 (1985)

    Article  PubMed  CAS  Google Scholar 

  45. Bacon, K.B.: Chemokine Induced Signal Transduction in Leukocyte. Chemokine and Their Receptor: From Basic Research to Therapeutic Intervention. Institute Pasteur, Paris, France (1999)

    Google Scholar 

  46. Hommes, D.W., Peppelenbosch, M.P., van Deventer, S.J.: Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut. 52, 144–151 (2003)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

Varun Kesherwani is CSIR-SRF.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ajit Sodhi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sodhi, A., Kesherwani, V. Production of TNF-α, IL-1β, IL-12 and IFN-γ in murine peritoneal macrophages on treatment with wheat germ agglutinin in vitro: involvement of tyrosine kinase pathways. Glycoconj J 24, 573–582 (2007). https://doi.org/10.1007/s10719-007-9054-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-007-9054-z

Keywords

Navigation