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COX-2 as a multifunctional neuronal modulator

Nature Medicine volume 7, pages 414–415 (2001)Cite this article

COX-2 is involved in prostaglandin synthesis and expressed throughout the nervous system, where it participates in pain sensitivity and in synaptic plasticity. Microsomal prostaglandin E synthase, expressed throughout the nervous system microvasculature, may be another important player in neural aspects of the inflammatory response.

Biosynthesis of PGE2 requires the enzyme prostaglandin E synthase (PGES). Ek et al.1 cloned the microsomal form of PGES (mPGES) from rat and investigated its expression in the CNS after injection of IL-1β. The authors were able to detect expression of PGES in the cerebral blood vessels up to five hours after IL-1β administration, which matches the time course for PGE2 induction. The induction of PGES was preceded by induction of COX-2 expression. Using an elegant dual in situ hybridization technique, they demonstrated that COX-2 and mPGES mRNAs colocalized within the same vascular endothelial cells and also in perivascular macrophages. Ek et al. showed that most of the endothelial cells expressing mPGES mRNA and COX-2 mRNA also expressed the type I IL-1β receptor. They propose that during the inflammatory response, circulating IL-1β induces synthesis of PGE2, which acts on prostaglandin E receptors in the nervous system parenchyma to induce cellular responses.

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Figure 1: Regulatory checkpoints of peripheral pain hypersensitivity and of systemic inflammation.

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  1. Neuroscience Center and Department of Ophthalmology School of Medicine Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA

    Nicolas G. Bazan

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Bazan, N. COX-2 as a multifunctional neuronal modulator. Nat Med 7, 414–415 (2001). https://doi.org/10.1038/86477

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