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. 1996 Jan 15;313(Pt 2):519–524. doi: 10.1042/bj3130519

Differential induction of the mitogen-activated protein kinase pathway by bacterial lipopolysaccharide in cultured monocytes and astrocytes.

S A Willis 1, P D Nisen 1
PMCID: PMC1216937  PMID: 8573086

Abstract

We recently reported that cyclic AMP (cAMP) specifically inhibits lipopolysaccharide (LPS)-induced interleukin 1 beta (IL-1 beta) transcription initiation in astrocytic cells but enhances the LPS induction of IL-1 beta in monocytic cells. The purpose of this study was to determine how cAMP differentially regulates LPS-induced IL-1 beta transcription in these two cell types. Two essential components of the mitogen-activated protein (MAP) kinase signal-transduction pathway, extracellular-signal-regulated kinase (ERK2; p41 mapk) and Raf-1, have been shown to be targets of LPS stimulation in other cell types, and therefore may be linked to the regulation of IL-1 beta transcription. In the human astrocytic cell line, U-373MG, LPS was found to strongly activate (and cAMP to inhibit) both ERK2 and Raf-1. In the human monocytic cell line, THP-1, LPS minimally activated ERK2 and did not activate Raf-1. These findings suggest that, in astrocytic cells, elevated intracellular cAMP levels may negatively regulate LPS activation of IL-1 beta via the MAP kinase signalling pathway. In contrast, this pathway is not significantly activated by LPS in monocytic cells, thus inhibition by elevated intracellular cAMP levels would not affect IL-1 beta transcription.

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Selected References

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

  1. Boulton T. G., Cobb M. H. Identification of multiple extracellular signal-regulated kinases (ERKs) with antipeptide antibodies. Cell Regul. 1991 May;2(5):357–371. doi: 10.1091/mbc.2.5.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boulton T. G., Nye S. H., Robbins D. J., Ip N. Y., Radziejewska E., Morgenbesser S. D., DePinho R. A., Panayotatos N., Cobb M. H., Yancopoulos G. D. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell. 1991 May 17;65(4):663–675. doi: 10.1016/0092-8674(91)90098-j. [DOI] [PubMed] [Google Scholar]
  3. Cook S. J., McCormick F. Inhibition by cAMP of Ras-dependent activation of Raf. Science. 1993 Nov 12;262(5136):1069–1072. doi: 10.1126/science.7694367. [DOI] [PubMed] [Google Scholar]
  4. Curran T., Franza B. R., Jr Fos and Jun: the AP-1 connection. Cell. 1988 Nov 4;55(3):395–397. doi: 10.1016/0092-8674(88)90024-4. [DOI] [PubMed] [Google Scholar]
  5. Davis R. J. The mitogen-activated protein kinase signal transduction pathway. J Biol Chem. 1993 Jul 15;268(20):14553–14556. [PubMed] [Google Scholar]
  6. Dinarello C. A. Role of interleukin-1 in infectious diseases. Immunol Rev. 1992 Jun;127:119–146. doi: 10.1111/j.1600-065x.1992.tb01411.x. [DOI] [PubMed] [Google Scholar]
  7. Dong Z., Qi X., Fidler I. J. Tyrosine phosphorylation of mitogen-activated protein kinases is necessary for activation of murine macrophages by natural and synthetic bacterial products. J Exp Med. 1993 Apr 1;177(4):1071–1077. doi: 10.1084/jem.177.4.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fenton M. J., Clark B. D., Collins K. L., Webb A. C., Rich A., Auron P. E. Transcriptional regulation of the human prointerleukin 1 beta gene. J Immunol. 1987 Jun 1;138(11):3972–3979. [PubMed] [Google Scholar]
  9. Fierz W., Endler B., Reske K., Wekerle H., Fontana A. Astrocytes as antigen-presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation. J Immunol. 1985 Jun;134(6):3785–3793. [PubMed] [Google Scholar]
  10. Finco T. S., Baldwin A. S., Jr Kappa B site-dependent induction of gene expression by diverse inducers of nuclear factor kappa B requires Raf-1. J Biol Chem. 1993 Aug 25;268(24):17676–17679. [PubMed] [Google Scholar]
  11. Frey E. A., Miller D. S., Jahr T. G., Sundan A., Bazil V., Espevik T., Finlay B. B., Wright S. D. Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992 Dec 1;176(6):1665–1671. doi: 10.1084/jem.176.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Han J., Lee J. D., Bibbs L., Ulevitch R. J. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science. 1994 Aug 5;265(5173):808–811. doi: 10.1126/science.7914033. [DOI] [PubMed] [Google Scholar]
  13. Hiscott J., Marois J., Garoufalis J., D'Addario M., Roulston A., Kwan I., Pepin N., Lacoste J., Nguyen H., Bensi G. Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol Cell Biol. 1993 Oct;13(10):6231–6240. doi: 10.1128/mcb.13.10.6231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lange-Carter C. A., Pleiman C. M., Gardner A. M., Blumer K. J., Johnson G. L. A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science. 1993 Apr 16;260(5106):315–319. doi: 10.1126/science.8385802. [DOI] [PubMed] [Google Scholar]
  15. Lee S. C., Collins M., Vanguri P., Shin M. L. Glutamate differentially inhibits the expression of class II MHC antigens on astrocytes and microglia. J Immunol. 1992 Jun 1;148(11):3391–3397. [PubMed] [Google Scholar]
  16. Mordret G. MAP kinase kinase: a node connecting multiple pathways. Biol Cell. 1993;79(3):193–207. doi: 10.1016/0248-4900(93)90138-5. [DOI] [PubMed] [Google Scholar]
  17. Morrison D. 14-3-3: modulators of signaling proteins? Science. 1994 Oct 7;266(5182):56–57. doi: 10.1126/science.7939645. [DOI] [PubMed] [Google Scholar]
  18. Mustafa M. M., Lebel M. H., Ramilo O., Olsen K. D., Reisch J. S., Beutler B., McCracken G. H., Jr Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. J Pediatr. 1989 Aug;115(2):208–213. doi: 10.1016/s0022-3476(89)80067-8. [DOI] [PubMed] [Google Scholar]
  19. Nakajima T., Kinoshita S., Sasagawa T., Sasaki K., Naruto M., Kishimoto T., Akira S. Phosphorylation at threonine-235 by a ras-dependent mitogen-activated protein kinase cascade is essential for transcription factor NF-IL6. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2207–2211. doi: 10.1073/pnas.90.6.2207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Northwood I. C., Gonzalez F. A., Wartmann M., Raden D. L., Davis R. J. Isolation and characterization of two growth factor-stimulated protein kinases that phosphorylate the epidermal growth factor receptor at threonine 669. J Biol Chem. 1991 Aug 15;266(23):15266–15276. [PubMed] [Google Scholar]
  21. Radler-Pohl A., Sachsenmaier C., Gebel S., Auer H. P., Bruder J. T., Rapp U., Angel P., Rahmsdorf H. J., Herrlich P. UV-induced activation of AP-1 involves obligatory extranuclear steps including Raf-1 kinase. EMBO J. 1993 Mar;12(3):1005–1012. doi: 10.1002/j.1460-2075.1993.tb05741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rossomando A., Wu J., Weber M. J., Sturgill T. W. The phorbol ester-dependent activator of the mitogen-activated protein kinase p42mapk is a kinase with specificity for the threonine and tyrosine regulatory sites. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5221–5225. doi: 10.1073/pnas.89.12.5221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Roth R. I., Levin J., Behr S. A modified Limulus amebocyte lysate test with increased sensitivity for detection of bacterial endotoxin. J Lab Clin Med. 1989 Sep;114(3):306–311. [PubMed] [Google Scholar]
  24. Seger R., Ahn N. G., Boulton T. G., Yancopoulos G. D., Panayotatos N., Radziejewska E., Ericsson L., Bratlien R. L., Cobb M. H., Krebs E. G. Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6142–6146. doi: 10.1073/pnas.88.14.6142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shirakawa F., Saito K., Bonagura C. A., Galson D. L., Fenton M. J., Webb A. C., Auron P. E. The human prointerleukin 1 beta gene requires DNA sequences both proximal and distal to the transcription start site for tissue-specific induction. Mol Cell Biol. 1993 Mar;13(3):1332–1344. doi: 10.1128/mcb.13.3.1332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sung S. S., Walters J. A. Increased cyclic AMP levels enhance IL-1 alpha and IL-1 beta mRNA expression and protein production in human myelomonocytic cell lines and monocytes. J Clin Invest. 1991 Dec;88(6):1915–1923. doi: 10.1172/JCI115515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tsukada J., Saito K., Waterman W. R., Webb A. C., Auron P. E. Transcription factors NF-IL6 and CREB recognize a common essential site in the human prointerleukin 1 beta gene. Mol Cell Biol. 1994 Nov;14(11):7285–7297. doi: 10.1128/mcb.14.11.7285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Velasco S., Tarlow M., Olsen K., Shay J. W., McCracken G. H., Jr, Nisen P. D. Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1 beta and tumor necrosis factor alpha expression in cultured human astroglial cells by dexamethasone and indomethacin. J Clin Invest. 1991 May;87(5):1674–1680. doi: 10.1172/JCI115184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Weinstein S. L., Sanghera J. S., Lemke K., DeFranco A. L., Pelech S. L. Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages. J Biol Chem. 1992 Jul 25;267(21):14955–14962. [PubMed] [Google Scholar]
  30. Willis S. A., Nisen P. D. Inhibition of lipopolysaccharide-induced IL-1 beta transcription by cyclic adenosine monophosphate in human astrocytic cells. J Immunol. 1995 Feb 1;154(3):1399–1406. [PubMed] [Google Scholar]
  31. Wright S. D., Ramos R. A., Tobias P. S., Ulevitch R. J., Mathison J. C. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990 Sep 21;249(4975):1431–1433. doi: 10.1126/science.1698311. [DOI] [PubMed] [Google Scholar]
  32. Wu J., Dent P., Jelinek T., Wolfman A., Weber M. J., Sturgill T. W. Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3',5'-monophosphate. Science. 1993 Nov 12;262(5136):1065–1069. doi: 10.1126/science.7694366. [DOI] [PubMed] [Google Scholar]

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