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Immunoregulation

Mediating endotoxin tolerance

Nature Reviews Immunology volume 4, page 750 (2004)Cite this article

LPS binds to Toll-like receptor 4 (TLR4) and stimulates two signalling pathways — a myeloid differentiation primary-response gene 88 (MyD88)-dependent pathway and a MyD88-independent pathway — both of which lead to activation of nuclear factor-κB (NF-κB). Based on studies showing that NF-κB activation is reduced in endotoxin tolerance and that SHIP inhibits the NF-κB pathway in bone-marrow-derived mast cells stimulated with IgE plus antigen, the authors decided to investigate the role of SHIP in endotoxin tolerance.

SHIP-deficient mice were shown to be more susceptible to LPS-induced toxicity than wild-type mice. The SHIP-deficient mice produced considerably increased amounts of pro-inflammatory cytokines and nitric oxide, indicating that SHIP is a negative regulator of LPS-induced production of inflammatory mediators. In contrast to wild-type cells, bone-marrow-derived macrophages and mast cells from SHIP-deficient mice did not show endotoxin tolerance.

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References

ORIGINAL RESEARCH PAPER

  1. Sly, L. M., Rauh, M. J., Kalesnikoff, J., Song, C. H. & Krystal, G. LPS-induced upregulation of SHIP is essential for endotoxin tolerance. Immunity 21, 227–239 (2004).

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FURTHER READING

  1. Beutler, B. & Rietschel, E. T. Innate immune sensing and its roots: the story of endotoxin. Nature Rev. Immunol. 3, 169–176 (2003).

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Authors
  1. Elaine Bell
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Bell, E. Mediating endotoxin tolerance. Nat Rev Immunol 4, 750 (2004). https://doi.org/10.1038/nri1463

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  • DOI: https://doi.org/10.1038/nri1463

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