Abstract
Fraction 1 (F1) protein forms a capsule on the surface of Yersinia pestis. Recently, we reported rF1-induced activation of macrophages. In current investigation, we studied the role of JNK MAPK signal transduction pathway in rF1-induced activation of macrophages in vitro. SP600125, a specific inhibitor of JNK, inhibited JNK MAPK phosphorylation, indicating the specificity of the above response. Though, the rF1-induced phosphorylation of JNK MAPK was also inhibited by upstream protein kinase C inhibitor H7, tyrosine kinase inhibitor genestein and PI3-K inhibitor wotmannin. Activation of the transcription factor NF-kB (phosphorylation of IkB) and c-Jun was observed in response to rF1 treatment. The rF1-induced JNK MAPK activity was correlated to the functional activation of macrophages by demonstrating the inhibition of NO, TNF-α production and microtubule polymerization caused by SP600125. Taken together, the data suggests the involvement of JNK MAPK/NF-kB pathway in rF1-induced activation of macrophages.
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Cornelis GR, Boland A, Boyd AP, Geuijen C, Iriarte M, Neyt C, Sory MP, Stainier I: The virulence plasmid of yersinia, an antihost genome. Microbiol Mol Biol Rev 62:1315–1352, 1998
Simonet M, Richard S, Berche P: Electron microscopic evidence for in vivo extracellular localization of Yersinia pseudotuberculosis harboring the pYV plasmid. Infect Immun 59:841–845, 1990
Cornelis GR: How Yops find their way out of Yersinia. Mol Microbiol 50:1091–1094, 2003
Galan JE, Collmer A: Type III secretion machines: bacterial devices for protein delivery into host cells. Science 284:1322–1328, 1999
Cornelis GR: The Yersinia deadly kiss. J Bacteriol 180:5495–4504, 1998
Protsenko OA, Anisimov PI, Mosarov OT, Donnov NP, Popov YA, Kokushkin AM: Detection and characterization of Yersinia pestis plasmids determining pesticin 1 fraction 1 antigen and mouse toxin synthesis. Genetica 19:1081–1090, 1983
Cherepanov PA, Mikhailova TG, Karimova GA, Zakharova NM, Ershov Y, Volvoi KI: Clonning and detailed mapping of the pFra-ymt region of the Yersinia pestis plasmid pFra. Mol Gen Mikrobiol Virusol 18:19–26, 1991
Brown SD, Montie TC: Beta-adrenergic blocking activity of Yersinia pestis murine toxin. Infect Immun 12:85–93, 1977
Brubaker RR: Factors promoting acute and chronic disease caused by yersiniae. Clin Microbiol Rev 4:309–324, 1991
Galyov EE, Smirnov O, Karlishev AV, Volvoi KI, Denesyuk AI, Nazimov IV, Rubtsov KS, Abramov VM, Dalvadyanz SM, Zavyalov VP: Nucleotide sequence of the Yersinia pestis gene encoding F1 antigen and the primary structure of the protein: Putative T cell and B cell epitopes. FEBS Lett 257:230–232, 1990
Galyov EE, Karlishev AV, Chernovskaya TV, Dolgikh DA, Smirnov O, Volvoi KI, Abramov VM, Zavyalov VP: Expression of the envelope antigen F1 of Yersinia pestis is mediated by the product of the Caf1M gene having homology with the chaperon protein Pap D of Escherichia coli. FEBS Lett 286:79–82, 1991
Karlishev AV, Galyov EE, Smirnov O, Gazayev AP, Abramov VM, Zavyalov VP: A new gene of the f1 operon of Y. pestis is involved in the capsule biogenesis. FEBS Lett 297:77–80, 1992
Sabhnani L, Rao DN: Identification of immunodominant epitope of F1 antigen of Yersinia pestis. FEMS Immunol Med Microbiol 27:155–162, 2002
Isupov IV, Nazarova LS, Pavlova LP, Gor’kova AV, Revazova ES, Dushkin VA, Zadumina S, Surikov NN, Taranenko TM, Dzhaparidze MN, et al.: The effect of different Yersinia pestis antigens on the cellular link in immunity. Zh Mikrobiol Epidemiol Immunobiol 9:82–89, 1990
Grebtsova NN, Cherniavskaia AS, Lebedeva SA, Ivanova VS: The phagocytic activity of peritoneal macrophages in relation to Yersinia pestis with defective and complete Fra genes. Zh Mikrobiol Epidemiol Immunobiol 5:7–11, 1990
Vasilleva GI, Deroshenko EP, Kiseleva AK: Changes in the “latent” virulence of a vaccinal strain of Yersinia pestis multiplying within macrophages. Zh Mikrobiol Epidemiol Immunobiol 9:63–66, 1988
Blenis J: Signal transduction via the MAP kinases: Proceed at your Own RSK. Proc Natl Acad Sci 90:5889–5892, 1993
Chang L, Karin M: Mammalian MAP Kinase signaling cascades. Nature 410:37–40, 2001
Dong C, Davis RJ, Flavell RA: MAP Kinases in the immune response. Annu Rev Immunol 20:55–72, 2002
Lee FS, Hagler J, Chen ZJ, Maniatis T: Activation of the IκBα kinase complex by MEKK1, a kinase of the JNK pathway. Cell 88:213–222, 1997
Kyriakis JM, Avruch J: Mammalian Mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869, 2001
Hirano M, Osada S, Aoki T, Hirai S, Hosaka M, Inoue J: MEK kinase involved in tumor necrosis factor α-induced NF-κB activation and degradation of IκB-α. J Biol Chem 271: 13234–13238, 1996
Wright SD, Kolesnick RN: Does endotoxin stimulate cells by mimicking ceramide? Immunol Today 16:297–302, 1995
Adams DO, Hamilton TA: The Cell biology of macrophages activation. Annu Rev Immunol 2:283–318, 1984
Adams DO, Hamilton TA, Macrophages as destructive cells in host defense. In JI Gallin, IM Goldstein, R Snyderman (eds). Inflammation Basic Principles and Clinical Correlates. 2nd edn. New York, Raven press, 1992, pp 637–662
Germain RN, Margulies DH: The biochemistry and cell biology of antigen processing and presentation. Annu Rev Immunol 11:403–450, 1993
Ding A, Chen B, Fuortes M, Blum E: Association of mitogen-activated protein kinases with microtubules in mouse macrophages. J Exp Med 183:1899–1904, 1996
Sodhi A, Singh RK, Singh SM: Effect of IFN-γ priming of murine peritoneal macrophages on the activation of tumoricidal state by IL-1, TNF and cisplatin. Clin Exp Immunol 888:350–355, 1992
Mizel SB: Interleukin and T-cell activation. Immunol Rev 63:51–72, 1982
Sodhi A, Sharma RK, Batra HV, Tuteja U: Recombinant Fraction 1 protein of Y. pestis activates murine peritoneal macrophages in vitro. Cell Immunol 229:52–61, 2004
Sharma RK, Sodhi A, Batra HV, Tuteja U: Effect of rLcrV and rYopB from Yersinia pestis on murine peritoneal macrophages in vitro. Immunol Lett 93:179–187, 2004
Sodhi A, Biswas SK: fMLP-induced in vitro nitric oxide production and its regulation in murine peritoneal macrophages. J Leukoc Biol 71:262–270, 2002
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
Chan ED, Winston BW, Uh ST, Wynes MW, Rose DM, Riches DW: Evaluation of the role of mitogen-activated protein kinases in the expression of inducible nitric oxide synthase by IFN-gamma and TNF-alpha in mouse macrophages. J Immunol 162:415–422, 1999
Kukharskyy V, Sulimenko V, Macurek L, Sulimenko T, Draberova E, Draber P: Complexes of gamma-tubulin with nonreceptor protein tyrosine kinases Src and Fyn in differentiating P19 embryonal carcinoma cells. Exp Cell Res 298:218–228, 2004
Chang L, Jones Y, Ellisman MH, Goldstein LS, Karin M: JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev Cell 4:521–533, 2003
Huang C, Jacobson K, Schaller MD: MAP kinases and cell migration. J Cell Sci 117:4619–4628, 2004
Kirikae T, Kirikae F, Oghiso Y, Nakano M: Microtubule-disrupting agents inhibit nitric oxide production in murine peritoneal macrophages stimulated with lipopolysaccharide or paclitaxel (Taxol). Infect Immun 64:3379–3384, 1996
Damiani MT, Colombo MI: Microfilaments and microtubules regulate recycling from phagosomes. Exp Cell Res 289:152–161, 2003
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Sharma, R.K., Sodhi, A. & Batra, H.V. Involvement of c-Jun N-Terminal Kinase in rF1 Mediated Activation of Murine Peritoneal Macrophages In Vitro. J Clin Immunol 25, 215–223 (2005). https://doi.org/10.1007/s10875-005-4087-1
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DOI: https://doi.org/10.1007/s10875-005-4087-1