The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice
Neurokinin (NK) signaling is involved in various inflammatory processes. A common manifestation of systemic inflammation is fever, which is usually induced in animal models with the administration of bacterial lipopolysaccharide (LPS). A role for the NK1 receptor was shown in LPS-induced fever, but...
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00166/full |
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| author | Eszter Pakai Eszter Pakai Valeria Tekus Valeria Tekus Csaba Zsiboras Zoltan Rumbus Emoke Olah Patrik Keringer Nora Khidhir Robert Matics Laszlo Deres Laszlo Deres Katalin Ordog Katalin Ordog Nikolett Szentes Nikolett Szentes Krisztina Pohoczky Krisztina Pohoczky Agnes Kemeny Agnes Kemeny Peter Hegyi Peter Hegyi Peter Hegyi Erika Pinter Erika Pinter Andras Garami |
| author_facet | Eszter Pakai Eszter Pakai Valeria Tekus Valeria Tekus Csaba Zsiboras Zoltan Rumbus Emoke Olah Patrik Keringer Nora Khidhir Robert Matics Laszlo Deres Laszlo Deres Katalin Ordog Katalin Ordog Nikolett Szentes Nikolett Szentes Krisztina Pohoczky Krisztina Pohoczky Agnes Kemeny Agnes Kemeny Peter Hegyi Peter Hegyi Peter Hegyi Erika Pinter Erika Pinter Andras Garami |
| author_sort | Eszter Pakai |
| collection | DOAJ |
| description | Neurokinin (NK) signaling is involved in various inflammatory processes. A common manifestation of systemic inflammation is fever, which is usually induced in animal models with the administration of bacterial lipopolysaccharide (LPS). A role for the NK1 receptor was shown in LPS-induced fever, but the underlying mechanisms of how the NK1 receptor contributes to febrile response, especially in the early phase, have remained unknown. We administered LPS (120 µg/kg, intraperitoneally) to mice with the Tacr1 gene, i.e., the gene encoding the NK1 receptor, either present (Tacr1+/+) or absent (Tacr1−/−) and measured their thermoregulatory responses, serum cytokine levels, tissue cyclooxygenase-2 (COX-2) expression, and prostaglandin (PG) E2 concentration. We found that the LPS-induced febrile response was attenuated in Tacr1−/− compared to their Tacr1+/+ littermates starting from 40 min postinfusion. The febrigenic effect of intracerebroventricularly administered PGE2 was not suppressed in the Tacr1−/− mice. Serum concentration of pyrogenic cytokines did not differ between Tacr1−/− and Tacr1+/+ at 40 min post-LPS infusion. Administration of LPS resulted in amplification of COX-2 mRNA expression in the lungs, liver, and brain of the mice, which was statistically indistinguishable between the genotypes. In contrast, the LPS-induced augmentation of COX-2 protein expression was attenuated in the lungs and tended to be suppressed in the liver of Tacr1−/− mice compared with Tacr1+/+ mice. The Tacr1+/+ mice responded to LPS with a significant surge of PGE2 production in the lungs, whereas Tacr1−/− mice did not. In conclusion, the NK1 receptor is necessary for normal fever genesis. Our results suggest that the NK1 receptor contributes to the early phase of LPS-induced fever by enhancing COX-2 protein expression in the periphery. These findings advance the understanding of the crosstalk between NK signaling and the “cytokine-COX-2-prostaglandin E2” axis in systemic inflammation, thereby open up the possibilities for new therapeutic approaches. |
| first_indexed | 2024-04-12T01:18:29Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T01:18:29Z |
| publishDate | 2018-02-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-24fb3661dfb040a48e9cd7f553bf51662022-12-22T03:53:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00166331420The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in MiceEszter Pakai0Eszter Pakai1Valeria Tekus2Valeria Tekus3Csaba Zsiboras4Zoltan Rumbus5Emoke Olah6Patrik Keringer7Nora Khidhir8Robert Matics9Laszlo Deres10Laszlo Deres11Katalin Ordog12Katalin Ordog13Nikolett Szentes14Nikolett Szentes15Krisztina Pohoczky16Krisztina Pohoczky17Agnes Kemeny18Agnes Kemeny19Peter Hegyi20Peter Hegyi21Peter Hegyi22Erika Pinter23Erika Pinter24Andras Garami25Institute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryMomentum Gastroenterology Multidisciplinary Research Group, Hungarian Academy of Sciences – University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Pecs, HungaryJanos Szentagothai Research Centre, University of Pecs, Pecs, HungaryInstitute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryInstitute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryInstitute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryInstitute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryInstitute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryInstitute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryJanos Szentagothai Research Centre, University of Pecs, Pecs, HungaryFirst Department of Medicine, Medical School, University of Pecs, Pecs, HungaryJanos Szentagothai Research Centre, University of Pecs, Pecs, HungaryFirst Department of Medicine, Medical School, University of Pecs, Pecs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Pecs, HungaryJanos Szentagothai Research Centre, University of Pecs, Pecs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Pecs, HungaryJanos Szentagothai Research Centre, University of Pecs, Pecs, HungaryJanos Szentagothai Research Centre, University of Pecs, Pecs, HungaryDepartment of Medical Biology, Medical School, University of Pecs, Pecs, HungaryInstitute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryMomentum Gastroenterology Multidisciplinary Research Group, Hungarian Academy of Sciences – University of Szeged, Szeged, HungaryFirst Department of Medicine, University of Szeged, Szeged, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Pecs, HungaryJanos Szentagothai Research Centre, University of Pecs, Pecs, HungaryInstitute for Translational Medicine, Medical School, University of Pecs, Pecs, HungaryNeurokinin (NK) signaling is involved in various inflammatory processes. A common manifestation of systemic inflammation is fever, which is usually induced in animal models with the administration of bacterial lipopolysaccharide (LPS). A role for the NK1 receptor was shown in LPS-induced fever, but the underlying mechanisms of how the NK1 receptor contributes to febrile response, especially in the early phase, have remained unknown. We administered LPS (120 µg/kg, intraperitoneally) to mice with the Tacr1 gene, i.e., the gene encoding the NK1 receptor, either present (Tacr1+/+) or absent (Tacr1−/−) and measured their thermoregulatory responses, serum cytokine levels, tissue cyclooxygenase-2 (COX-2) expression, and prostaglandin (PG) E2 concentration. We found that the LPS-induced febrile response was attenuated in Tacr1−/− compared to their Tacr1+/+ littermates starting from 40 min postinfusion. The febrigenic effect of intracerebroventricularly administered PGE2 was not suppressed in the Tacr1−/− mice. Serum concentration of pyrogenic cytokines did not differ between Tacr1−/− and Tacr1+/+ at 40 min post-LPS infusion. Administration of LPS resulted in amplification of COX-2 mRNA expression in the lungs, liver, and brain of the mice, which was statistically indistinguishable between the genotypes. In contrast, the LPS-induced augmentation of COX-2 protein expression was attenuated in the lungs and tended to be suppressed in the liver of Tacr1−/− mice compared with Tacr1+/+ mice. The Tacr1+/+ mice responded to LPS with a significant surge of PGE2 production in the lungs, whereas Tacr1−/− mice did not. In conclusion, the NK1 receptor is necessary for normal fever genesis. Our results suggest that the NK1 receptor contributes to the early phase of LPS-induced fever by enhancing COX-2 protein expression in the periphery. These findings advance the understanding of the crosstalk between NK signaling and the “cytokine-COX-2-prostaglandin E2” axis in systemic inflammation, thereby open up the possibilities for new therapeutic approaches.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00166/fullfeverthermoregulationsystemic inflammationendotoxincyclooxygenaseautonomic thermoeffectors |
| spellingShingle | Eszter Pakai Eszter Pakai Valeria Tekus Valeria Tekus Csaba Zsiboras Zoltan Rumbus Emoke Olah Patrik Keringer Nora Khidhir Robert Matics Laszlo Deres Laszlo Deres Katalin Ordog Katalin Ordog Nikolett Szentes Nikolett Szentes Krisztina Pohoczky Krisztina Pohoczky Agnes Kemeny Agnes Kemeny Peter Hegyi Peter Hegyi Peter Hegyi Erika Pinter Erika Pinter Andras Garami The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice Frontiers in Immunology fever thermoregulation systemic inflammation endotoxin cyclooxygenase autonomic thermoeffectors |
| title | The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice |
| title_full | The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice |
| title_fullStr | The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice |
| title_full_unstemmed | The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice |
| title_short | The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice |
| title_sort | neurokinin 1 receptor contributes to the early phase of lipopolysaccharide induced fever via stimulation of peripheral cyclooxygenase 2 protein expression in mice |
| topic | fever thermoregulation systemic inflammation endotoxin cyclooxygenase autonomic thermoeffectors |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00166/full |
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