ArticleProceedings of the National Academy of Sciences of the United States of America2006
IL-15 mediates immune inflammatory hypernociception by triggering a sequential release of IFN-gamma, endothelin, and prostaglandin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 66 citations in OpenAlex.
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- Pregabalin inhibits proinflammatory cytokine release in patients with fibromyalgia syndrome.Archives of rheumatology · 2023Article
- Immune Actions on the Peripheral Nervous System in Pain.International journal of molecular sciences · 2021Review
- IL-15 and IL15RA in Osteoarthritis: Association With Symptoms and Protease Production, but Not Structural Severity.Frontiers in immunology · 2020Article
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- Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway.Frontiers in immunology · 2020Article
- Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation.Mediators of inflammation · 2019Article
- Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor in the chronic phase of a mouse model of complex regional pain syndrome type I.Pflugers Archiv : European journal of physiology · 2018Article
- The Sesquiterpene Lactone, Budlein A, Inhibits Antigen-Induced Arthritis in Mice: Role of NF-κB and Cytokines.Inflammation · 2017Article
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- Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- The ruthenium nitric oxide donor, [Ru(HEDTA)NO], inhibits acute nociception in mice by modulating oxidative stress, cytokine production and activating the cGMP/PKG/ATP-sensitive potassium channel signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- IL-33/ST2 signalling contributes to carrageenin-induced innate inflammation and inflammatory pain: role of cytokines, endothelin-1 and prostaglandin E2.British journal of pharmacology · 2013Article
- Th1-Th17 cells contribute to the development of uropathogenic Escherichia coli-induced chronic pelvic pain.PloS one · 2013Article
- Interactions between the immune and nervous systems in pain.Nature medicine · 2010Article
- Article
- Fructose-1,6-bisphosphate reduces inflammatory pain-like behaviour in mice: role of adenosine acting on A1 receptors.British journal of pharmacology · 2009Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
IL-15 is closely associated with inflammatory diseases. IL-15 targeting is effective in treating experimental and clinical rheumatoid arthritis (RA). Because hyperalgesia accompanies RA, we investigated the ability of IL-15 to induced nociceptor sensitization (hypernociception). We report here that IL-15 induced time- and dose-dependent mechanical hypernociception in mice. IL-15-induced hypernociception was inhibited by treatment with a dual endothelin receptor type A (ET(A))/endothelin receptor type B (ET(B)) antagonist (bosentan), ET(A) receptor antagonist (BQ123), or cyclooxygenase inhibitor (indomethacin). Moreover, IL-15 failed to induce hypernociception in IFN-gamma(-/-) mice, suggesting that IL-15 mediated hypernociception via an IFN-gamma-, endothelin (ET)-, and prostaglandin-dependent pathway. Consistent with this finding, IFN-gamma and ET-1 induced dose- and time-dependent mechanical hypernociception that was inhibited by BQ123 or indomethacin but not BQ788 (an ET(B) receptor antagonist). IFN-gamma induced the production of ET-1 and the expression of its mRNA precursor (preproET-1, PPET-1). Moreover, IL-15 also induced ET-1 production and PPET-1 mRNA expression in an IFN-gamma-dependent manner. Prostaglandin E(2) (PGE(2)) production was induced by IL-15, IFN-gamma, or ET-1. We also found that hypernociception induced by ovalbumin (OVA) in OVA-immunized mice was significantly diminished by treatment with sIL-15Ralpha (soluble IL-15 receptor alpha-chain), bosentan, BQ123, or indomethacin. Furthermore, OVA challenge induced the expression of PPET-1 mRNA in WT mice but not in IFN-gamma(-/-) mice. The PPET-1 mRNA expression was also inhibited by sIL-15Ralpha pretreatment. Therefore, our results demonstrate the sequential mechanical hypernociceptive effect of IL-15 --> IFN-gamma --> ET-1 --> PGE(2) and suggest that these molecules may be targets of therapeutic intervention in antigen-induced hypernociception.
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