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5-Lipoxygenase and leukotriene A4 hydrolase expression in primary nephrotic syndrome

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Abstract

Gene expression of 5-lipoxygenase (5-LO) and leukotriene A4 (LTA4) hydrolase was analyzed in the peripheral blood of 48 children with active primary nephrotic syndrome (PNS) (group I), 27 children with PNS in remission (group II), and 20 controls. Group I included 34 patients with steroid-sensitive PNS (SSNS) and 14 patients with steroid-resistant PNS (SRNS). Total RNA purified from peripheral blood mononuclear (PBMN) cells was reverse transcribed into cDNA and amplified with specific primers in the polymerase chain reaction. All group I patients and none of the controls expressed 5-LO and LTA4 hydrolase. Of group II children, 22.2% expressed 5-LO, while 51.9% expressed LTA4 hydrolase. Among group I patients there was a significant positive correlation between the degree of proteinuria and the expression of 5-LO (r=0.27, P=0.03) and LTA4 hydrolase (r=0.44, P=0.001). There was no difference in the degree of expression of both enzymes between SSNS and SRNS patients. In conclusion, leukotrienes may play a role in the pathogenesis of PNS in children, but they do not participate in the response of these patients to steroids.

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References

  1. Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237:1171–1176

    CAS  PubMed  Google Scholar 

  2. Henderson WR (1994) The role of leukotrienes in inflammation. Ann Intern Med 121:684–697

    CAS  PubMed  Google Scholar 

  3. Lewis RA, Austen KF, Soberman RJ (1991) Leukotrienes and other products of the 5-lipoxygenase pathway. N Engl J Med 323:645–652

    Google Scholar 

  4. Badr KF (1991) Arachidonic acid metabolites in glomerular injury. Semin Nephrol 11:332–339

    CAS  PubMed  Google Scholar 

  5. Dixon RAF, Jones RE, Diehl R, Bennett CD, Kargman S, Rouzer CA (1988) Cloning of the cDNA for human 5-lipoxygenase. Proc Nat Acad Sci USA 85:416–420

    CAS  Google Scholar 

  6. International Study of Kidney Disease in Children (ISKDC) (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 98:561–564

    PubMed  Google Scholar 

  7. Menegatti E, Roccatello D, Hadden K, Piccoli G, De Rosa G, Sena LM, Rifai A (1999) Gene expression of 5-lipoxygenase and LTA4 hydrolase in renal tissue of nephrotic syndrome patients. Clin Exp Immunol 116:347–353

    Article  CAS  PubMed  Google Scholar 

  8. Shindo M, Mullin GE, Braun-Elwert L, Bergasa NV, Jones EA James SP (1996) Cytokine mRNA expression in the liver of patients with primary biliary cirrhosis (PBC) and chronic hepatitis B (CHB). Clin Exp Immunol 105:254–259

    Article  CAS  PubMed  Google Scholar 

  9. Badr KF (1997) Glomerulonephritis: roles for lipoxygenase pathways in pathophysiology and therapy. Curr Opin Hypertens Nephrol 6:111–118

    CAS  Google Scholar 

  10. Brady HR, O’Meara YM (1997) Lipoxins, leukocyte recruitment and the resolution phase of acute glomerulonephritis. Kidney Int [Suppl] 58:56–61

    Google Scholar 

  11. Nassar GM, Badr KF (1995) Role of leukotrienes and lipoxygenases in glomerular injury. Miner Electrolyte Metab 21:262–270

    CAS  PubMed  Google Scholar 

  12. Brady HR, Serhan CN (1992) Adhesion promotes transcellular leukotriene biosynthesis during neutrophils-glomerular endothelial cell interactions: inhibition by antibodies against CD18 andl-selectin. Biochem Biophys Res Commun 186:1307–1314

    CAS  PubMed  Google Scholar 

  13. Rifai A, Sakai H, Yagame M (1993) Expression of 5-lipoxygenase and 5-lipoxygenase activation protein in glomerulonephritis. Kidney Int 43 [Suppl 39]:S95–S99

    Google Scholar 

  14. Lianos EA (1988) Synthesis of hydroxyeicosatetraenoic acids leukotrienes in rat nephrotoxic serum glomerulonephritis. Role of anti-glomerular basement membrane antibody dose, complement, and neutrophils. J Clin Invest 82:427–435

    CAS  PubMed  Google Scholar 

  15. Rahman MA, Nakazawa M, Emancipator SN, Dunn MJ (1988) Increased leukotriene B4 synthesis in immune injured rat glomeruli. J Clin Invest 81:1945–1952

    CAS  PubMed  Google Scholar 

  16. Lefkowith JB, Nagamatsu T, Pippin J, Schreiner JF (1991) Role of leukocytes in metabolic and functional derangements of experimental glomerulonephritis. Am J Physiol 261:F213–F220

    CAS  PubMed  Google Scholar 

  17. Petric R, Ford-Hutchison AW (1994) Elevated cysteinyl leukotriene excretion in experimental glomerulonephritis. Kidney Int 46:1322–1329

    CAS  PubMed  Google Scholar 

  18. Petric R, Ford-Hutchinson AW (1995) Inhibition of leukotriene biosynthesis improves renal function in experimental glomerulonephritis. J Lipid Med 11:231–240

    Article  CAS  Google Scholar 

  19. Valdivielso JM, Montero A, Badr KF, Munger KA (2003) Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats. J Nephrol 16:85–94

    CAS  PubMed  Google Scholar 

  20. Guasch A, Zayas CF, Badr KF (1999) MK-591 acutely restores glomerular size selectivity and reduces proteinuria in human glomerulonephritis. Kidney Int 56:261–267

    Article  CAS  PubMed  Google Scholar 

  21. Serhan CN (1997) Lipoxins and novel aspirin-triggered 15-epi-lipoxins: a jungle of cell-cell interactions or a therapeutic opportunity. Prostaglandins 53:107–137

    Article  CAS  PubMed  Google Scholar 

  22. Wenzel SE (1997) Arachidonic acid metabolites: mediators of inflammation in asthma. Pharmacotherapy 17:35–125

    Google Scholar 

  23. Albrightson CR, Short B, Dytko G, Zabko-Potapovich B, Brickson B, Adams JL, Griswold DE (1994) Selective inhibition of 5-lipoxygenase attenuates glomerulonephritis in the rat. Kidney Int 45:1301–1310

    CAS  PubMed  Google Scholar 

  24. Takahashi K, Kato T, Schreiner GF, Ebert J, Badr KF (1992) Essential fatty acid deficiency normalizes function and histology in rat nephrotoxic serum nephritis. Kidney Int 41:1245–1253

    CAS  PubMed  Google Scholar 

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Bakr, A., Hawas, S., Slem, S. et al. 5-Lipoxygenase and leukotriene A4 hydrolase expression in primary nephrotic syndrome. Pediatr Nephrol 19, 396–399 (2004). https://doi.org/10.1007/s00467-003-1399-3

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  • DOI: https://doi.org/10.1007/s00467-003-1399-3

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