Abstract
The effects of lipopolysaccharide (LPS) and several cytokines on the c-fos and c-jun mRNA expression were examined in primary cultured astrocytes. Either LPS (500 ng/mL) or interferon-γ (IFN-γ; 5 ng/mL) alone increased the level of c-fos mRNA (1 h). However, tumor necrosis factor-α (TNF-α; 10 ng/mL) or interleukin-1β (IL-1β; 5 ng/mL) alone showed no significant induction of the level of c-fos mRNA. TNF-α showed a potentiating effect in the regulation of LPS-induced c-fos mRNA expression, whereas LPS showed an inhibitory action against IFN-γ-inducedc-fos mRNA expression. LPS, but not TNF-α, IL-β and IFN-γ, increased the level of c-jun mRNA (1 h). TNF-α and IFN-γ showed an inhibitory action against LPS-induced c-jun mRNA expression. Both phorbol 12-myristate 13-acetate (PMA; 2.5 mM) and forskolin (FSK; 5 mM) increased the c-fos and c-jun mRNA expressions. In addition, the level of c-fos mRNA was expressed in an antagonistic manner when LPS was combined with PMA. When LPS was co-treated with either PMA or FSK, it showed an additive interaction for the induction of c-jun mRNA expression. Our results suggest that LPS and cytokines may be actively involved in the regulation of c-fos andc-jun mRNA expressions in primary cultured astrocytes. Moreover, both the PKA and PKC pathways may regulate the LPS-induced c-fos and c-jun mRNA expressions in different ways.
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References
Ahmad, M., Theofanidis, P., and Medford, R.M., Role of activating protein-1 in the regulation of the vascular cell adhesion molecule-1 gene expression by tumor necrosis factor-alpha.J. Biol. Chem., 273, 4616–4621 (1998).
Arenander, A., de Vellis, and J., Early response gene induction in astrocytes as a mechanism for encoding and integrating neuronal signals.Prog. Brain Res., 94, 177–188 (1994).
Barnea, A., Roberts, J., Keller, P., and Word, R.A., Interleukin-1beta induces expression of neuropeptide Y in primary astrocyte cultures in a cytokine-specific manner: induction in human but not rat astrocytes.Brain Res., 896, 137–145 (2001).
Bertani, A., Polentarutti, N., Sica, A., Rambaldi, A., Mantovani, A., Colotta, and F., Expression of c-jun protooncogene in human myelomonocytic cells.Blood, 74, 1811–1816 (1989).
Bohman, D., Bos, T.J., Admon, A., Nishimura, T., Vogt, P.K., Tjian, and R., Human protooncogene c-jun encodes a DNA-binding protein with structural and functional properties of transcription factor AP-1.Science, 238, 1386–1392 (1987).
Brenner, D.A., O’Hara, M., Angel, P., Chojkier, M., and Karin, M., Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha.Nature, 337, 661–663 (1989).
Cheshire, J.L. and Baldwin, A.S. {jrJr.}, Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferonvia enhanced I kappaB alpha degradation and de novo I kappaB beta degradation.Mol. Cell Biol., 17, 6746–6754 (1997).
Cheshire, J.L., Williams, B.R., and Baldwin, A.S. {jrJr.}, Involvement of double-stranded RNA-activated protein kinase in the synergistic activation of nuclear factor-kappaB by tumor necrosis factor-alpha and gamma-interferon in preneuronal cells.J. Biol. Chem., 274, 4801–4806 (1999).
Chomczynski, P. and Sacchi, N., Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal. Biochem., 162, 156–159 (1987).
Conca, W., Kaplan, P.B., and Krane, S.M., Increases in levels of procollagenase messenger RNA in cultured fibroblasts induced by human recombinant interleukin 1 beta or serum follow c-jun expression and are dependent on new protein synthesis.J. Clin. Invest., 83, 1753–1757 (1989).
Curran, T., Gordon, M.B., Rubino, K.L., and Sambucetti, L.C., Isolation and characterization ofc-fos (rat) cDNA and analysis of post-translational modificationin vitro.Oncogene, 2, 79–84 (1987).
Danielson, P.E., Forss-Petter, S., Brow, M.A., Calavetta, L., Douglass, J., Milner, R.J., and Sutchliffe, J.G., p1B15: a cDNA clone of the rat mRNA encoding cyclophilin.DNA, 7, 261–267 (1988).
Dokter, W.H., Esselink, M.T., Halie, M.R., and 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, 81, 337–343 (1993).
Friedman, W.J., Altiok, N., Fredholm, B.B., and Persson, H., Mechanisms of nerve growth factor mRNA regulation by interieukin-1 beta in hippocampal cultures: role of second messengers.J. Neurosci. Res., 33, 37–46 (1992).
Goldring, M.B., Birkhead, J.R., Suen, L.F., Yamin, R., Mizuno, S., Glowacki, J., Arbiser, J.L., and Apperley, J.F., Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes.J. Clin. Invest., 94, 2307–2316 (1994).
Granger, R.L., Hughes, T.R., Ramji, and D.P., Gene, stimulus and cell-type specific regulation of activator protein-1 in mesangial cells by lipopolysaccharide and cytokines.Biochim. Biophys. Acta, 1492, 100–107 (2000).
Kim, Y.H., Choi, M.R., Song, D.K., Huh, S.O., Jang, C.G., and Suh, H.W., Regulation of c-fos gene expression by lipopolysaccharide and cycloheximide in C6 rat glioma cells.Brain Res., 28, 227–230 (2000).
Koerner, T.J., Adams, D.O., and Hamilton, T.A., Regulation of tumor necrosis factor (TNF) expression: interferon-gamma enhances the accumulation of mRNA for TNF induced by lipopolysaccharide in murine peritoneal macrophages.Cell Immunol., 109, 437–443 (1987).
Kopchik, T.T., Cullen, R., and Stacey, D.W., Rapid analysis of small nucleic acid samples by gel electrophoresis.Anal. Biochem., 115, 419–423 (1981).
Landschulz, W.H., Johnson, P.F., and McKnight, S.L., The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins.Science, 240, 1759–1764 (1988).
Lee, J.K., Choi, S.S., Won, J.S., and Suh, H.W., The Regulation of inducible nitric oxide synthase gene expression induced by lipopolysaccharide plus tumor necrosis factor-a in C6 cells: the involvements of AP-1 and NFκB.Life Sci., 73, 595–609 (2003).
Lee, J.K., Won, J.S., Choi, M.R., Kim, Y.H., and Suh, H.W., Differential effects of forskolin and phorbol 12-myristate-13-acetate on the c-fos and c-jun mRNA expression in rat C6 glioma cells.Mol. Cells, 12, 11–16 (2001).
Morrison, D.C. and Ryan, J.L., Endotoxins and disease mechanisms.Annu. Rev. Med., 38, 417–432 (1987).
Paludan, S.R., Synergistic action of pro-inflammatory agents: cellular and molecular aspects.J. Leukoc. Biol., 67, 18–25 (2000).
Rajaram, N. and Kerppola, T.K., DNA bending by Fos-Jun and the orientation of heterodimer binding depend on the sequence of the AP-1 site.EMBO J., 16, 2917–2925 (1997).
Robinson, M.J. and Cobb, M.H., Mitogen-activated protein kinase pathways.Curr. Opin. Cell Biol., 9, 180–186 (1997).
Rubio, N., Interferon-gamma induces the expression of immediate early genes c-fos and c-jun in astrocytes.Immunology, 91, 560–564 (1997).
Ryuto, M., Ono, M., Izumi, H., Yoshida, S., Weich, H.A., Kohno, K., and Kuwano, M., Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells. Possible roles of SP-1.J. Biol. Chem., 271, 28220–28228 (1996).
Sheng, M. and Greenberg, M.E., The regulation and function of c-fos and other immediate early genes in the nerve system.Neuron, 4, 477–485 (1990).
Simi, A., Ingelman-Sundberg, M., and Tindberg, N., Neuroprotective agent chlomethiazole attenuates c-fos, c-jun, and AP-1 activation through inhibition of p38 MAP kinase.J. Cereb. Blood Flow Metab., 20, 1077–1088 (2000).
Takahashi, N., Hayano, T., and Suzuki, M., Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin.Nature, 337, 473–475 (1989).
Tengku-Muhammad, T.S., Hughes, T.R., Foka, P., Cryer, A., and Ramji, D.P., Cytokine-mediated differential regulation of macrophage activator protein-1 genes.Cytokine, 12, 720–726 (2000).
Vilijn, M.H., Vaysse, P.J., Zukin, R.S., and Kessler, J.A., Expression of preproenkephlalin mRNA by cultured astrocytes and neurons.Proc. Natl. Acad. Sci. U.S.A., 85, 6551–6553 (1988).
Won, J.S., Song, D.K., Kim, Y.H., Huh, S.O., and Suh, H.W., The stimulation of rat astrocytes with phorbol-12-myristate-13-acetate increases the proenkephalin mRNA: involvement of proto-oncogenes.Brain Res. Mol. Brain Res., 54, 288–297 (1998).
Won, J.S. and Suh, H.W., The differential molecular mechanisms underlying proenkephalin mRNA expression induced by forskolin and phorbol-12-myristic-13-acetate in primary cultured astrocytes.Brain Res. Mol. Brain Res., 84, 41–51 (2000).
Yu, A.C., Lee, Y.L., Fu, W.Y., and Eng, L.F., Gene expression in astrocytes during and after ischemia.Prog. Brain Res., 105, 245–253 (1995).
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Suh, HW., Choi, SS., Lee, JK. et al. Regulation of c-fos and c-jun gene expression by lipopolysaccharide and cytokines in primary cultured astrocytes: effect of PKA and PKC pathways. Arch Pharm Res 27, 396–401 (2004). https://doi.org/10.1007/BF02980080
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DOI: https://doi.org/10.1007/BF02980080