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Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis

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Abstract

We studied the febrile response in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal isomerase expressed in cytokine-sensitive brain endothelial cells. These animals showed no fever and no central prostaglandin (PG) E2 synthesis after peripheral injection of bacterial-wall lipopolysaccharide, but their pyretic capacity in response to centrally administered PGE2 was intact. Our findings identify mPGES-1 as the central switch during immune-induced pyresis and as a target for the treatment of fever and other PGE2-dependent acute phase reactions elicited by the brain.

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Figure 1: Febrile response following peripheral immune challenge.
Figure 2: PGE2 levels and synthesis after immune challenge in Ptges+/+ and Ptges−/− mice 3 h after i.p. injection of LPS or saline.
Figure 3: PGE2-induced febrile response.

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Acknowledgements

Supported by the Swedish Research Council (07879, 14706 and 12573) and Cancer Foundation (4095). We thank B. Koller for the gift of EP3–deficient mice.

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Authors and Affiliations

  1. Division of Cell Biology, Faculty of Health Sciences, University of Linköping, Linköping, S-581 85, Sweden

    David Engblom, Linda Engström & Anders Blomqvist

  2. Center for Structural Biochemistry, Karolinska Institute, Huddinge, 141 57, Sweden

    Sipra Saha

  3. Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, 171 77, Sweden

    Marie Westman & Per-Johan Jakobsson

  4. Inflammation Unit, Pfizer Global Research and Development, Groton Laboratories, Groton, 06340, Connecticut, USA

    Laurent P Audoly

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  1. David Engblom
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  2. Sipra Saha
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  3. Linda Engström
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  4. Marie Westman
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  5. Laurent P Audoly
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  6. Per-Johan Jakobsson
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  7. Anders Blomqvist
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Correspondence to Anders Blomqvist.

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Engblom, D., Saha, S., Engström, L. et al. Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis. Nat Neurosci 6, 1137–1138 (2003). https://doi.org/10.1038/nn1137

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