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The signal transduction pathway that mediates the effect of interleukin-1 beta on the Na+-K+-ATPase in LLC-PK1 cells

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Abstract

IL-1β reduces the activity and protein expression of Na+-K+-ATPase in rat kidney cells. The aim of the present study was to elucidate the signalling pathway involved, using the LLC-PK1 cell line. In these cells IL-1β caused a time and concentration-dependent decrease in the protein expression of the Na+-K+-ATPase. Inhibition of extracellular signal-regulated kinase (ERK), nuclear factor-κB (NF-κB) and cyclooxygenase (COX), but not p38 mitogen-activated kinase (MAPK), abolished the effect of the cytokine on the pump. The activation of NF-κB by IL-1β was maximal at 20 min and declined thereafter. Inhibition of the transcription factor by pyrrolidinediethyldithiocarbamate (PDTC) down-regulated the ATPase. The effects of IL-1β on the pump and NF-κB were prevented by the COX inhibitor indomethacin. Exogenous PGE2 reduced protein expression of the ATPase within 15 min, even in presence of an ERK inhibitor. It is concluded that IL-1β stimulates the mitogen and extracellular signal regulated protein kinase kinase/extracellular signal regulated protein kinase (MEK/ERK) pathway. This activates NF-κB, thus leading to increased COX-2 expression and PGE2 release. PGE2 in turn inhibits NF-κB and reduces the protein expression of Na+-K+-ATPase.

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References

  1. Al-Sadi R, Kreydiyyeh SI (2003) Mediators of interleukin-1 beta action on the Na+K+-ATPase in Caco-2 cells. Eur Cytokine Netw 14:83–90

    CAS  PubMed  Google Scholar 

  2. Barnes PJ (1997). Nuclear factor-kappa B. Int J Biochem Cell Biol 29:867–870

    Article  CAS  PubMed  Google Scholar 

  3. Beasley D, Dinarello CA, Cannon JG (1988) Interleukin-1 induces natriuresis in conscious rats: role of renal prostaglandins. Kidney Int l33:1050–1065

    Google Scholar 

  4. Caverzasio J, Rizzoli R, Dayer JM, Bonjour JP (1987) Interleukin-1 decreases renal Na+ reabsorption: possible mechanism of endotoxin-induced natriuresis. Am J Physiol 252:F943–F946

    CAS  PubMed  Google Scholar 

  5. Chibalin AV, Katz AI, Berggre PO, Bertorello AM (1998) Receptor-mediated inhibition of renal Na+-K+-ATPase is associated with endocytosis of its alpha and beta-subunits. Am J Physiol 273:C1458–C1465

    Google Scholar 

  6. Chen G, Wood EG, Wang SH, Warner TD (1999) Expression of cyclooxygenase-2 in rat vascular smooth muscle cells is unrelated to nuclear factor-κB activation. Life Sci 64:1231–1242

    Article  CAS  PubMed  Google Scholar 

  7. Cohen-Luria R, Moran A, Rimon G (1994) Cyclooxygenase inhibitors suppress inhibitory effect of PGE2 on Na-K-ATPase in MDCK cells. Am J Physiol 267:F94–F98

    CAS  PubMed  Google Scholar 

  8. Crambert G, Hasler U, Beggah AT, Yu C, Modyanov N, Horisberger JD, Lelievre L, Geering K (2000) Transport and pharmacological properties of nine different human Na,K-ATPase isozymes. J Biol Chem 275:1976–1986

    Article  CAS  PubMed  Google Scholar 

  9. Diaz A, Chepenik KP, Korn JH, Reginato AM, Jimenez SA (1998) Differential regulation of cyclooxygenases 1 and 2 by interlukin-1 beta, tumor necrosis factor-alpha, and transforming growth factor-beta 1 in human lung fibroblasts. Exp Cell Res 241:222–229

    Article  CAS  PubMed  Google Scholar 

  10. Dinarello CA (2000) Proinflammatory cytokines. Chest 118:503–508

    CAS  PubMed  Google Scholar 

  11. Eder J (1997) Tumour necrosis factor alpha and interleukin 1 signalling: do MAPKK kinases connect it all? Trends Pharmacol Sci 18:319–322

    Article  CAS  PubMed  Google Scholar 

  12. Guan Z, Buckman SY, Miller BW, Springer LD, Morrison AR (1998) Interleukin-1 beta-induced cyclooxygnease-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. J Biol Chem 273:28670–28676

    CAS  PubMed  Google Scholar 

  13. Husted RF, Zhang C, Stokes JB (1998) Concerted actions of IL-1β inhibit Na+ absorption and stimulate anion secretion by IMCD cells. Am J Physiol 275:F946–F954

    CAS  PubMed  Google Scholar 

  14. Jiang B, Brecher P, Cohen RA (2001) Persistent activation of nuclear factor-κB by interleukin-1 beta and subsequent inducible NO synthase expression requires extracellular signal-regulated kinase. Arterioscler Thromb Casc Biol 21:1915–1920

    CAS  Google Scholar 

  15. Kohan DE, Merli CA, Simon EE (1989) Micropuncture localization of the natriuretic effect of interleukin-1. Am J Physiol 256:F810–F813

    CAS  PubMed  Google Scholar 

  16. Kreydiyyeh S, Al-Sadi R (2002) Interluekin-1β increases urine flow rate and inhibits protein expression of Na+/K+ ATPase in the rat jejunum and kidney. J Interferon Cytokine Res 22:1041–1048

    Article  CAS  PubMed  Google Scholar 

  17. Laporte JD, Moore PE, Lahiri T, Schwartzman IN, Panettieri RA Jr, Shore SA (2000) P38 MAP kinase regulates IL-1 beta responses in cultured airway smooth muscle cells. Am. J Physiol 279:L932–L941

    CAS  Google Scholar 

  18. Leung K, Betts JC, Xu L, Nabel GJ (1994) The cytoplasmic domain of the interleukin-1 receptor is required for nuclear factor-kappa B signal transduction. J. Biol Chem 269:1579–1582

    CAS  Google Scholar 

  19. Lingrel JB, Kuntzweiler T (1994) Na+-K+-ATPase. J Biol Chem 209:19659–19662

    Google Scholar 

  20. Poligone B, Baldwin AS (2001) Positive an negative regulation of NF-kappa B by COX-2: roles of different prostaglandins. J Biol Chem 42:38658–38664

    Article  Google Scholar 

  21. Rothwarf DM, Karin M (1999) The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleus. Sci STKE 26:RE1

    Google Scholar 

  22. Sakairi Y, Ando Y, Tabei K, Kusano E, Asano Y (1994) Interleukin-1 inhibits Na+ and water transport in rabbit cortical collecting duct. Am J Physiol 266:F674–F680

    CAS  PubMed  Google Scholar 

  23. Saklatvala J, Dean J, Finch A (1999) Protein kinase cascades in intracellular signaling by interleukin-I and tumour necrosis factor. Biochem Soc Symp 64:63–77

    CAS  PubMed  Google Scholar 

  24. Schulze-Osthoff K, Ferrari D, Riehemann K, Wesselborg S (1997) Regulation of NF-kappa B activation by MAP kinase cascades. Immunobiology 198:35–49

    CAS  PubMed  Google Scholar 

  25. Skou JC, Esmann M (1992). The Na,K-ATPase. J Bioenerg Biomembr 24:249–261

    CAS  PubMed  Google Scholar 

  26. Stylianou E, O’Neill LA, Rawlinson L, Edbrooke MR, Woo P, Saklatvala J (1992) Interleukin 1 induces NF-kappa B through its type I but not its type II receptor in lymphocytes. J. Biol Chem 267:15836–15841

    CAS  Google Scholar 

  27. Smith WL, DeWitt DL, Garavito RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145–182

    Article  CAS  PubMed  Google Scholar 

  28. Taussky HH, Shorr E (1953) Microcolorimetric method for determination of inorganic phosphorous. J Biol Chem 202:675–685

    CAS  PubMed  Google Scholar 

  29. Vane JR, Bakhle YS, Botting RM (1998) Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120

    CAS  PubMed  Google Scholar 

  30. Zeidel ML, Brady HR, Kohan DE (1991) Interleukin-1 inhibition of Na+-K+-ATPase in inner medullary collecting duct cells: role of PGE2. Am J Physiol 261:F1013–F1016

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported from a grant from the University Research Board and the National Lebanese Council for Scientific Research.

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Authors and Affiliations

  1. Department of Biology, Faculty of Arts & Sciences, American University of Beirut, Beirut, Lebanon

    Sawsan Ibrahim Kreydiyyeh & Rana Al-Sadi

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  1. Sawsan Ibrahim Kreydiyyeh
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  2. Rana Al-Sadi
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Correspondence to Sawsan Ibrahim Kreydiyyeh.

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Kreydiyyeh, S.I., Al-Sadi, R. The signal transduction pathway that mediates the effect of interleukin-1 beta on the Na+-K+-ATPase in LLC-PK1 cells. Pflugers Arch - Eur J Physiol 448, 231–238 (2004). https://doi.org/10.1007/s00424-004-1242-0

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  • DOI: https://doi.org/10.1007/s00424-004-1242-0

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