Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1997 Jul 1;325(Pt 1):223–228. doi: 10.1042/bj3250223

Involvement of diacylglycerol production in activation of nuclear factor kappaB by a CD14-mediated lipopolysaccharide stimulus.

H Yamamoto 1, K Hanada 1, M Nishijima 1
PMCID: PMC1218549  PMID: 9224650

Abstract

Exposure of Chinese hamster CHO-K1 transfectant cells expressing mouse CD14 (CHO/CD14 cells) to lipopolysaccharide (LPS) induced rapid elevation of the cellular diacylglycerol (DAG) and choline/phosphocholine levels and nuclear translocation of nuclear factor kappaB (NFkappaB). When cells were incubated with short-chain DAG analogues or bacterial phospholipase C, NFkappaB activation occurred even without the LPS stimulus. Treatment of CHO/CD14 cells with tricyclo[5.2.1.0(2.6)]decyl-(9[8])xanthogenate (D609), an inhibitor of phosphatidylcholine-specific phospholipase C and phospholipase D, almost completely inhibited not only the LPS-dependent production of DAG and choline/phosphocholine but also the LPS-dependent NFkappaB activation. In contrast, treatment of cells with 1-(6-¿[3-methoxyoestra-1,3, 5(10)-trien-17beta-yl]-1H-pyrrole-2,5-dione (U73122), an inhibitor of phosphatidylinositol-specific phospholipase C in vitro, did not affect the LPS-dependent activation of NFkappaB. Production of DAG and activation of NFkappaB after the LPS stimulus were observed in mouse macrophage-like J774.1 cells, and this response to LPS by J774. 1 cells was also inhibited by D609. These results suggest that the production of DAG from phosphatidylcholine was upstream of NFkappaB activation in response to a CD14-mediated LPS stimulus.

Full Text

The Full Text of this article is available as a PDF (334.9 KB).

Selected References

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

  1. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  2. Davis S., Aldrich T. H., Stahl N., Pan L., Taga T., Kishimoto T., Ip N. Y., Yancopoulos G. D. LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science. 1993 Jun 18;260(5115):1805–1808. doi: 10.1126/science.8390097. [DOI] [PubMed] [Google Scholar]
  3. Delude R. L., Fenton M. J., Savedra R., Jr, Perera P. Y., Vogel S. N., Thieringer R., Golenbock D. T. CD14-mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity. J Biol Chem. 1994 Sep 2;269(35):22253–22260. [PubMed] [Google Scholar]
  4. Divecha N., Irvine R. F. Phospholipid signaling. Cell. 1995 Jan 27;80(2):269–278. doi: 10.1016/0092-8674(95)90409-3. [DOI] [PubMed] [Google Scholar]
  5. Dunlop M., Clark S. Activation of phospholipase D in CHO cells transfected with the human epidermal growth factor (EGF) receptor: differential effects of protein kinase C activation and EGF. Biochim Biophys Acta. 1993 Dec 16;1220(1):43–48. doi: 10.1016/0167-4889(93)90095-7. [DOI] [PubMed] [Google Scholar]
  6. Exton J. H. Phosphatidylcholine breakdown and signal transduction. Biochim Biophys Acta. 1994 Apr 14;1212(1):26–42. doi: 10.1016/0005-2760(94)90186-4. [DOI] [PubMed] [Google Scholar]
  7. Glauser M. P., Zanetti G., Baumgartner J. D., Cohen J. Septic shock: pathogenesis. Lancet. 1991 Sep 21;338(8769):732–736. doi: 10.1016/0140-6736(91)91452-z. [DOI] [PubMed] [Google Scholar]
  8. Hanada K., Izawa K., Nishijima M., Akamatsu Y. Sphingolipid deficiency induces hypersensitivity of CD14, a glycosyl phosphatidylinositol-anchored protein, to phosphatidylinositol-specific phospholipase C. J Biol Chem. 1993 Jul 5;268(19):13820–13823. [PubMed] [Google Scholar]
  9. Hara-Kuge S., Amano F., Nishijima M., Akamatsu Y. Isolation of a lipopolysaccharide (LPS)-resistant mutant, with defective LPS binding, of cultured macrophage-like cells. J Biol Chem. 1990 Apr 25;265(12):6606–6610. [PubMed] [Google Scholar]
  10. Haziot A., Ferrero E., Köntgen F., Hijiya N., Yamamoto S., Silver J., Stewart C. L., Goyert S. M. Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity. 1996 Apr;4(4):407–414. doi: 10.1016/s1074-7613(00)80254-x. [DOI] [PubMed] [Google Scholar]
  11. Hsu H., Xiong J., Goeddel D. V. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell. 1995 May 19;81(4):495–504. doi: 10.1016/0092-8674(95)90070-5. [DOI] [PubMed] [Google Scholar]
  12. Jing S., Wen D., Yu Y., Holst P. L., Luo Y., Fang M., Tamir R., Antonio L., Hu Z., Cupples R. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell. 1996 Jun 28;85(7):1113–1124. doi: 10.1016/s0092-8674(00)81311-2. [DOI] [PubMed] [Google Scholar]
  13. Kiss Z., Tomono M. Compound D609 inhibits phorbol ester-stimulated phospholipase D activity and phospholipase C-mediated phosphatidylethanolamine hydrolysis. Biochim Biophys Acta. 1995 Oct 26;1259(1):105–108. doi: 10.1016/0005-2760(95)00148-6. [DOI] [PubMed] [Google Scholar]
  14. Müller-Decker K. Interruption of TPA-induced signals by an antiviral and antitumoral xanthate compound: inhibition of a phospholipase C-type reaction. Biochem Biophys Res Commun. 1989 Jul 14;162(1):198–205. doi: 10.1016/0006-291x(89)91981-5. [DOI] [PubMed] [Google Scholar]
  15. Müller J. M., Ziegler-Heitbrock H. W., Baeuerle P. A. Nuclear factor kappa B, a mediator of lipopolysaccharide effects. Immunobiology. 1993 Apr;187(3-5):233–256. doi: 10.1016/S0171-2985(11)80342-6. [DOI] [PubMed] [Google Scholar]
  16. Nishijima M., Hara-Kuge S., Takasuka N., Akagawa K., Setouchi M., Matsuura K., Yamamoto S., Akamatsu Y. Identification of a biochemical lesion, and characteristic response to lipopolysaccharide (LPS) of a cultured macrophage-like cell mutant with defective LPS-binding. J Biochem. 1994 Nov;116(5):1082–1087. doi: 10.1093/oxfordjournals.jbchem.a124631. [DOI] [PubMed] [Google Scholar]
  17. Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992 Oct 23;258(5082):607–614. doi: 10.1126/science.1411571. [DOI] [PubMed] [Google Scholar]
  18. Schreiber E., Matthias P., Müller M. M., Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. doi: 10.1093/nar/17.15.6419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schütze S., Berkovic D., Tomsing O., Unger C., Krönke M. Tumor necrosis factor induces rapid production of 1'2'diacylglycerol by a phosphatidylcholine-specific phospholipase C. J Exp Med. 1991 Nov 1;174(5):975–988. doi: 10.1084/jem.174.5.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schütze S., Machleidt T., Krönke M. The role of diacylglycerol and ceramide in tumor necrosis factor and interleukin-1 signal transduction. J Leukoc Biol. 1994 Nov;56(5):533–541. doi: 10.1002/jlb.56.5.533. [DOI] [PubMed] [Google Scholar]
  21. Schütze S., Potthoff K., Machleidt T., Berkovic D., Wiegmann K., Krönke M. TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced "acidic" sphingomyelin breakdown. Cell. 1992 Nov 27;71(5):765–776. doi: 10.1016/0092-8674(92)90553-o. [DOI] [PubMed] [Google Scholar]
  22. Song J., Foster D. A. v-Src activates a unique phospholipase D activity that can be distinguished from the phospholipase D activity activated by phorbol esters. Biochem J. 1993 Sep 15;294(Pt 3):711–717. doi: 10.1042/bj2940711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sweet M. J., Hume D. A. Endotoxin signal transduction in macrophages. J Leukoc Biol. 1996 Jul;60(1):8–26. doi: 10.1002/jlb.60.1.8. [DOI] [PubMed] [Google Scholar]
  24. Thompson A. K., Mostafapour S. P., Denlinger L. C., Bleasdale J. E., Fisher S. K. The aminosteroid U-73122 inhibits muscarinic receptor sequestration and phosphoinositide hydrolysis in SK-N-SH neuroblastoma cells. A role for Gp in receptor compartmentation. J Biol Chem. 1991 Dec 15;266(35):23856–23862. [PubMed] [Google Scholar]
  25. Tobias P. S., Soldau K., Ulevitch R. J. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J Exp Med. 1986 Sep 1;164(3):777–793. doi: 10.1084/jem.164.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Treanor J. J., Goodman L., de Sauvage F., Stone D. M., Poulsen K. T., Beck C. D., Gray C., Armanini M. P., Pollock R. A., Hefti F. Characterization of a multicomponent receptor for GDNF. Nature. 1996 Jul 4;382(6586):80–83. doi: 10.1038/382080a0. [DOI] [PubMed] [Google Scholar]
  27. Vandenabeele P., Declercq W., Beyaert R., Fiers W. Two tumour necrosis factor receptors: structure and function. Trends Cell Biol. 1995 Oct;5(10):392–399. doi: 10.1016/s0962-8924(00)89088-1. [DOI] [PubMed] [Google Scholar]
  28. Wright S. D., Ramos R. A., Hermanowski-Vosatka A., Rockwell P., Detmers P. A. Activation of the adhesive capacity of CR3 on neutrophils by endotoxin: dependence on lipopolysaccharide binding protein and CD14. J Exp Med. 1991 May 1;173(5):1281–1286. doi: 10.1084/jem.173.5.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES