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PI3Kγ inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease generated by deregulation of T cell–mediated B-cell activation, which results in glomerulonephritis and renal failure. Disease is treated with immunosuppressants and cytostatic agents that have numerous side effects. Here we examine the use of inhibitors of phosphoinositide 3-kinase (PI3K) γ, a lipid kinase that regulates inflammation, in the MRL-lpr mouse model of SLE. Treatment reduced glomerulonephritis and prolonged lifespan, suggesting that P13Kγ may be a useful target in the treatment of chronic inflammation.

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Figure 1: p110γ inhibition reduces hypercellularity and PI3K-PKB pathway activity in MRL-lpr mice.
Figure 2: p110γ inhibition reduces renal disease and memory T-cell numbers in MRL-lpr mice.

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References

  1. Inghirami, G., Simon, J., Balow, J.E. & Tsokos, G.C. Clin. Exp. Rheumatol. 6, 269–276 (1988).

    CAS  PubMed  Google Scholar 

  2. Cervera, R., Jiménez, S., Font, J. & Ingelmo, M. J. Rheumatol. 6, 150–157 (2003).

    Google Scholar 

  3. Chatham, W.W. & Kimberly, R.P. Lupus 10, 140–147 (2001).

    Article  CAS  Google Scholar 

  4. Singer, G.G., Carrera, A.C., Marshak-Rothstein, A., Martinez-A.C. & Abbas, A.K. Curr. Opin. Immunol. 6, 913–920 (1994).

    Article  CAS  Google Scholar 

  5. Wakeland, E.K., Wandstrat, A.E., Liu, K. & Morel, L. Curr. Opin. Immunol. 11, 701–707 (1999).

    Article  CAS  Google Scholar 

  6. Dai, C., Liu, Z., Zhou, H. & Li, L. Chin. Med. J. 114, 864–868 (2001).

    CAS  PubMed  Google Scholar 

  7. Jevnikar, A.M., Grusby, M.J. & Glimcher, L.H. J. Exp. Med. 179, 1137–1143 (1994).

    Article  CAS  Google Scholar 

  8. Lang, T.J., Nguyen, P. & Papadimitriou, J.C. J. Immunol. 171, 5795–5801 (2003).

    Article  CAS  Google Scholar 

  9. Rodríguez-Borlado, L. et al. FASEB J. 14, 895–903 (2000).

    Article  Google Scholar 

  10. Neidhart, M., Pataki, F., Michel, B.A. & Fehr, K. Schweiz. Med. Wochenschr. 126, 1922–1925 (1996).

    CAS  PubMed  Google Scholar 

  11. Vanhaesebroeck, B., Ali, K., Bilancio, A., Geering, B. & Foukas, L.C. Trends Biochem. Sci. 30, 194–204 (2005).

    Article  CAS  Google Scholar 

  12. Niculescu, F. et al. Arthritis Rheum. 48, 1071–1079 (2003).

    Article  CAS  Google Scholar 

  13. Sasaki, T. et al. Science 287, 1040–1046 (2000).

    Article  CAS  Google Scholar 

  14. Hirsch, E. et al. Science 287, 1049–1053 (2000).

    Article  CAS  Google Scholar 

  15. Camps, M. et al. Nat. Med. 11, 936–943 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M.C. Moreno-Ortíz for cytofluorometry studies, P. Pallares, J. Martín and L. Gómez for animal work, A. Quadropani and the Serono team for technical advice and C. Mark for editorial assistance. D.F.B. has a Ramón y Cajal contract from the Spanish Ministry of Education and Science. This work was supported by grants from the Ramon Areces Fundation, European Union (QLRT2001-02171), the Community of Madrid (8.3/0030/2000) and the Spanish Dirección General de Ciencia y Desarrollo Tecnológico (SAF2001.2278). The Department of Immunology and Oncology was founded and is supported by the Spanish Council for Scientific Research and by Pfizer.

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Correspondence to Ana C Carrera.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Different cell types in splenocytes from Control, Dexamethasone- and AS605240-treated MRL-lpr mice. (PDF 412 kb)

Supplementary Fig. 2

Proportion and absolute numbers of memory cells in splenocytes from Control, Dexamethasone- and AS605240-treated MRL-lpr mice. (PDF 352 kb)

Supplementary Table 1

SLE-like disease in AS605240-treated MRL-lpr mice. (PDF 51 kb)

Supplementary Methods (PDF 88 kb)

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Barber, D., Bartolomé, A., Hernandez, C. et al. PI3Kγ inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus. Nat Med 11, 933–935 (2005). https://doi.org/10.1038/nm1291

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