Abstract
Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, inhibited in a dose-dependent manner (5-20 nM) the induction of C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen by interleukin-6 (IL-6) plus interleukin-1 (IL-1), and of fibrinogen by IL-6 alone, in Hep 3B cells. Induction of alpha 1-proteinase inhibitor (alpha 1-PI) by IL-6 plus IL-1 or IL-6 alone was not significantly affected by OA up to concentrations of 20 nM, above which concentration OA was toxic in Hep 3B cells. OA also inhibited the induction of CRP, fibrinogen and alpha 1-PI by IL-6 in the NPLC/PRF/5 cell line, albeit at a higher concentration (80 nM). These results suggest that the signal transduction mechanisms regulating induction of acute-phase proteins by IL-6, either alone or in combination with IL-1, are mediated by activation of protein phosphatases 1 and/or 2A.
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- Akira S., Hirano T., Taga T., Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990 Aug;4(11):2860–2867. [PubMed] [Google Scholar]
- Andus T., Geiger T., Hirano T., Northoff H., Ganter U., Bauer J., Kishimoto T., Heinrich P. C. Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-beta 2) regulates beta-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett. 1987 Aug 31;221(1):18–22. doi: 10.1016/0014-5793(87)80344-7. [DOI] [PubMed] [Google Scholar]
- Baumann H., Isseroff H., Latimer J. J., Jahreis G. P. Phorbol ester modulates interleukin 6- and interleukin 1-regulated expression of acute phase plasma proteins in hepatoma cells. J Biol Chem. 1988 Nov 25;263(33):17390–17396. [PMC free article] [PubMed] [Google Scholar]
- Baumann H., Prowse K. R., Marinković S., Won K. A., Jahreis G. P. Stimulation of hepatic acute phase response by cytokines and glucocorticoids. Ann N Y Acad Sci. 1989;557:280-95, discussion 295-6. doi: 10.1111/j.1749-6632.1989.tb24021.x. [DOI] [PubMed] [Google Scholar]
- Baumann H., Schendel P. Interleukin-11 regulates the hepatic expression of the same plasma protein genes as interleukin-6. J Biol Chem. 1991 Oct 25;266(30):20424–20427. [PubMed] [Google Scholar]
- Baumann H., Wong G. G. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J Immunol. 1989 Aug 15;143(4):1163–1167. [PubMed] [Google Scholar]
- Castell J. V., Gómez-Lechón M. J., David M., Hirano T., Kishimoto T., Heinrich P. C. Recombinant human interleukin-6 (IL-6/BSF-2/HSF) regulates the synthesis of acute phase proteins in human hepatocytes. FEBS Lett. 1988 May 23;232(2):347–350. doi: 10.1016/0014-5793(88)80766-x. [DOI] [PubMed] [Google Scholar]
- Cohen P., Holmes C. F., Tsukitani Y. Okadaic acid: a new probe for the study of cellular regulation. Trends Biochem Sci. 1990 Mar;15(3):98–102. doi: 10.1016/0968-0004(90)90192-e. [DOI] [PubMed] [Google Scholar]
- Fallon R. J. Staurosporine inhibits a tyrosine protein kinase in human hepatoma cell membranes. Biochem Biophys Res Commun. 1990 Aug 16;170(3):1191–1196. doi: 10.1016/0006-291x(90)90519-s. [DOI] [PubMed] [Google Scholar]
- Fey G. H., Gauldie J. The acute phase response of the liver in inflammation. Prog Liver Dis. 1990;9:89–116. [PubMed] [Google Scholar]
- Fujita-Yamaguchi Y., Kathuria S. Characterization of receptor tyrosine-specific protein kinases by the use of inhibitors. Staurosporine is a 100-times more potent inhibitor of insulin receptor than IGF-I receptor. Biochem Biophys Res Commun. 1988 Dec 30;157(3):955–962. doi: 10.1016/s0006-291x(88)80967-7. [DOI] [PubMed] [Google Scholar]
- Ganapathi M. K., Mackiewicz A., Samols D., Brabenec A., Kushner I., Schultz D., Hu S. I. Induction of C-reactive protein by cytokines in human hepatoma cell lines is potentiated by caffeine. Biochem J. 1990 Jul 1;269(1):41–46. doi: 10.1042/bj2690041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ganapathi M. K., May L. T., Schultz D., Brabenec A., Weinstein J., Sehgal P. B., Kushner I. Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines. Biochem Biophys Res Commun. 1988 Nov 30;157(1):271–277. doi: 10.1016/s0006-291x(88)80043-3. [DOI] [PubMed] [Google Scholar]
- Ganapathi M. K., Rzewnicki D., Samols D., Jiang S. L., Kushner I. Effect of combinations of cytokines and hormones on synthesis of serum amyloid A and C-reactive protein in Hep 3B cells. J Immunol. 1991 Aug 15;147(4):1261–1265. [PubMed] [Google Scholar]
- 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]
- Heinrich P. C., Castell J. V., Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990 Feb 1;265(3):621–636. doi: 10.1042/bj2650621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirano T., Akira S., Taga T., Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol Today. 1990 Dec;11(12):443–449. doi: 10.1016/0167-5699(90)90173-7. [DOI] [PubMed] [Google Scholar]
- Koj A. The role of interleukin-6 as the hepatocyte stimulating factor in the network of inflammatory cytokines. Ann N Y Acad Sci. 1989;557:1–8. doi: 10.1111/j.1749-6632.1989.tb23994.x. [DOI] [PubMed] [Google Scholar]
- Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci. 1982;389:39–48. doi: 10.1111/j.1749-6632.1982.tb22124.x. [DOI] [PubMed] [Google Scholar]
- Lord K. A., Abdollahi A., Thomas S. M., DeMarco M., Brugge J. S., Hoffman-Liebermann B., Liebermann D. A. Leukemia inhibitory factor and interleukin-6 trigger the same immediate early response, including tyrosine phosphorylation, upon induction of myeloid leukemia differentiation. Mol Cell Biol. 1991 Sep;11(9):4371–4379. doi: 10.1128/mcb.11.9.4371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackiewicz A., Ganapathi M. K., Schultz D., Brabenec A., Weinstein J., Kelley M. F., Kushner I. Transforming growth factor beta 1 regulates production of acute-phase proteins. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1491–1495. doi: 10.1073/pnas.87.4.1491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackiewicz A., Speroff T., Ganapathi M. K., Kushner I. Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines. J Immunol. 1991 May 1;146(9):3032–3037. [PubMed] [Google Scholar]
- Magielska-Zero D., Bereta J., Czuba-Pelech B., Pajdak W., Gauldie J., Koj A. Inhibitory effect of human recombinant interferon gamma on synthesis of acute phase proteins in human hepatoma Hep G2 cells stimulated by leukocyte cytokines, TNF alpha and IFN-beta 2/BSF-2/IL-6. Biochem Int. 1988 Jul;17(1):17–23. [PubMed] [Google Scholar]
- Mizel S. B. The interleukins. FASEB J. 1989 Oct;3(12):2379–2388. doi: 10.1096/fasebj.3.12.2676681. [DOI] [PubMed] [Google Scholar]
- Murakami M., Narazaki M., Hibi M., Yawata H., Yasukawa K., Hamaguchi M., Taga T., Kishimoto T. Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11349–11353. doi: 10.1073/pnas.88.24.11349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakajima K., Wall R. IL-6 induces hybridoma cell growth through a novel signalling pathway. Curr Top Microbiol Immunol. 1990;166:51–61. doi: 10.1007/978-3-642-75889-8_8. [DOI] [PubMed] [Google Scholar]
- Perlmutter D. H., Dinarello C. A., Punsal P. I., Colten H. R. Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest. 1986 Nov;78(5):1349–1354. doi: 10.1172/JCI112721. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramadori G., Sipe J. D., Dinarello C. A., Mizel S. B., Colten H. R. Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1. J Exp Med. 1985 Sep 1;162(3):930–942. doi: 10.1084/jem.162.3.930. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Resnitzky D., Tiefenbrun N., Berissi H., Kimchi A. Interferons and interleukin 6 suppress phosphorylation of the retinoblastoma protein in growth-sensitive hematopoietic cells. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):402–406. doi: 10.1073/pnas.89.1.402. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richards C. D., Brown T. J., Shoyab M., Baumann H., Gauldie J. Recombinant oncostatin M stimulates the production of acute phase proteins in HepG2 cells and rat primary hepatocytes in vitro. J Immunol. 1992 Mar 15;148(6):1731–1736. [PubMed] [Google Scholar]
- Taga T., Hibi M., Hirata Y., Yamasaki K., Yasukawa K., Matsuda T., Hirano T., Kishimoto T. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989 Aug 11;58(3):573–581. doi: 10.1016/0092-8674(89)90438-8. [DOI] [PubMed] [Google Scholar]



