Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 May 1;89(9):4071–4075. doi: 10.1073/pnas.89.9.4071

Manidipine regulates the transcription of cytokine genes.

M Roth 1, R Keul 1, L R Emmons 1, W H Hörl 1, L H Block 1
PMCID: PMC525634  PMID: 1570335

Abstract

Manidipine, a Ca(2+)-channel blocker, at concentrations that lower elevated blood pressure, modulates the transcription rates of cytokine genes in the mesangial cells of humans that had been stimulated with platelet-derived growth factor BB isomer; although the transcription for mRNA of interleukin 1 beta and granulocyte/monocyte colony-stimulating factor was inhibited, the transcription of mRNA for interleukin 6 was enhanced. Additionally, the induction of c-fos, c-jun, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase transcription was inhibited by manidipine. We conclude that manidipine, at nanomolar concentrations, is efficacious in modulating gene transcriptions that are involved in proinflammatory changes of mesangial cells. Thus, manidipine, at pharmacological concentrations that are one to two orders of magnitude lower than those required for inhibition of agonist- or depolarization (K+)-induced vasoconstriction, causes changes in the activity of the genes that code for inflammatory mediators.

Full text

PDF
4071

Images in this article

Selected References

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

  1. Abboud H. E., Poptic E., DiCorleto P. Production of platelet-derived growth factorlike protein by rat mesangial cells in culture. J Clin Invest. 1987 Sep;80(3):675–683. doi: 10.1172/JCI113121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angel P., Allegretto E. A., Okino S. T., Hattori K., Boyle W. J., Hunter T., Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. doi: 10.1038/332166a0. [DOI] [PubMed] [Google Scholar]
  3. Block L. H., Emmons L. R., Vogt E., Sachinidis A., Vetter W., Hoppe J. Ca2+-channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle cells. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2388–2392. doi: 10.1073/pnas.86.7.2388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Block L. H., Matthys H., Emmons L. R., Perruchoud A., Erne P., Roth M. Ca(2+)-channel blockers modulate expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and low density lipoprotein receptor genes stimulated by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9041–9045. doi: 10.1073/pnas.88.20.9041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chedid M., Yoza B. K., Brooks J. W., Mizel S. B. Activation of AP-1 by IL-1 and phorbol esters in T cells. Role of protein kinase A and protein phosphatases. J Immunol. 1991 Aug 1;147(3):867–873. [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Diamond J. R., Karnovsky M. J. Focal and segmental glomerulosclerosis: analogies to atherosclerosis. Kidney Int. 1988 May;33(5):917–924. doi: 10.1038/ki.1988.87. [DOI] [PubMed] [Google Scholar]
  8. Fellström B., Klareskog L., Heldin C. H., Larsson E., Rönnstrand L., Terracio L., Tufveson G., Wahlberg J., Rubin K. Platelet-derived growth factor receptors in the kidney--upregulated expression in inflammation. Kidney Int. 1989 Dec;36(6):1099–1102. doi: 10.1038/ki.1989.306. [DOI] [PubMed] [Google Scholar]
  9. Ferns G. A., Raines E. W., Sprugel K. H., Motani A. S., Reidy M. A., Ross R. Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science. 1991 Sep 6;253(5024):1129–1132. doi: 10.1126/science.1653454. [DOI] [PubMed] [Google Scholar]
  10. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Godfraind T., Miller R., Wibo M. Calcium antagonism and calcium entry blockade. Pharmacol Rev. 1986 Dec;38(4):321–416. [PubMed] [Google Scholar]
  12. Hass R., Brach M., Kharbanda S., Giese G., Traub P., Kufe D. Inhibition of phorbol ester-induced monocytic differentiation by dexamethasone is associated with down-regulation of c-fos and c-jun (AP-1). J Cell Physiol. 1991 Oct;149(1):125–131. doi: 10.1002/jcp.1041490116. [DOI] [PubMed] [Google Scholar]
  13. Lovett D. H., Larsen A. Cell cycle-dependent interleukin 1 gene expression by cultured glomerular mesangial cells. J Clin Invest. 1988 Jul;82(1):115–122. doi: 10.1172/JCI113558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mazzone T., Basheeruddin K., Ping L., Frazer S., Getz G. S. Mechanism of the growth-related activation of the low density lipoprotein receptor pathway. J Biol Chem. 1989 Jan 25;264(3):1787–1792. [PubMed] [Google Scholar]
  15. Nevins J. R. Isolation and analysis of nuclear RNA. Methods Enzymol. 1987;152:234–241. doi: 10.1016/0076-6879(87)52025-0. [DOI] [PubMed] [Google Scholar]
  16. Roth M., Emmons L. R., Perruchoud A., Block L. H. Expressions of the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase genes are stimulated by recombinant platelet-derived growth factor isomers. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1888–1892. doi: 10.1073/pnas.88.5.1888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ruef C., Budde K., Lacy J., Northemann W., Baumann M., Sterzel R. B., Coleman D. L. Interleukin 6 is an autocrine growth factor for mesangial cells. Kidney Int. 1990 Aug;38(2):249–257. doi: 10.1038/ki.1990.193. [DOI] [PubMed] [Google Scholar]
  18. Ryder K., Nathans D. Induction of protooncogene c-jun by serum growth factors. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8464–8467. doi: 10.1073/pnas.85.22.8464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schüle R., Evans R. M. Cross-coupling of signal transduction pathways: zinc finger meets leucine zipper. Trends Genet. 1991 Nov-Dec;7(11-12):377–381. doi: 10.1016/0168-9525(91)90259-s. [DOI] [PubMed] [Google Scholar]
  20. Sherman M. L., Stone R. M., Datta R., Bernstein S. H., Kufe D. W. Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells. J Biol Chem. 1990 Feb 25;265(6):3320–3323. [PubMed] [Google Scholar]
  21. Shultz P. J., DiCorleto P. E., Silver B. J., Abboud H. E. Mesangial cells express PDGF mRNAs and proliferate in response to PDGF. Am J Physiol. 1988 Oct;255(4 Pt 2):F674–F684. doi: 10.1152/ajprenal.1988.255.4.F674. [DOI] [PubMed] [Google Scholar]
  22. Sunderrajan S., Reams G., Bauer J. H. Renal effects of diltiazem in primary hypertension. Hypertension. 1986 Mar;8(3):238–242. doi: 10.1161/01.hyp.8.3.238. [DOI] [PubMed] [Google Scholar]
  23. Walz G., Zanker B., Barth C., Wieder K. J., Clark S. C., Strom T. B. Transcriptional modulation of human IL-6 gene expression by verapamil. J Immunol. 1990 Jun 1;144(11):4242–4248. [PubMed] [Google Scholar]
  24. Yoshimura A., Gordon K., Alpers C. E., Floege J., Pritzl P., Ross R., Couser W. G., Bowen-Pope D. F., Johnson R. J. Demonstration of PDGF B-chain mRNA in glomeruli in mesangial proliferative nephritis by in situ hybridization. Kidney Int. 1991 Sep;40(3):470–476. doi: 10.1038/ki.1991.234. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES