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Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages.
J Neuroimmunol. 2005 Aug; 165(1-2):139-49.JN

Abstract

Inflammation is a complex phenomenon involving multiple cellular and molecular interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical role in the inflammatory response and its over-expression has been associated with several pathologies including neurodegenerative diseases and cancer. Melatonin is the main product of the pineal gland with well documented antioxidant and immuno-modulatory effects. Since the action of the indole on COX-2 has not been previously described, the goal of the present report was to test the effect of melatonin on the activities of COX-2 and inducible nitric oxide synthase (iNOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2 activation induced by LPS, without affecting COX-1 protein levels. The structurally related compound 6-methoxy-melatonin only partially prevented the increase in COX-2 protein levels induced by the toxin. Likewise melatonin prevented iNOS activation and reduced the concentration of products from both enzymes, PGE(2) and nitric oxide. Another endogenous antioxidant like N-acetyl-cysteine (NAC) did not reduced COX-2 significantly. The current finding corroborates a role of melatonin as an anti-inflammatory agent and, for the first time, COX-2 and iNOS as molecular targets for either melatonin or its metabolites AFMK and AMK. These anti-inflammatory actions seem not to be exclusively mediated by the free radical scavenging properties of melatonin. As a consequence, the present work suggests these substances as a new class of potential anti-inflammatory agents without the classical side effects due to COX-1 inhibition.

Authors+Show Affiliations

Mayo JC
Departamento de Morfología y Biología Celular, Universidad de Oviedo, Asturias, España. mayojuan@uniovi.es
Sainz RM
No affiliation info available
Tan DX
No affiliation info available
Hardeland R
No affiliation info available
Leon J
No affiliation info available
Rodriguez C
No affiliation info available
Reiter RJ
No affiliation info available

MeSH

AnimalsAnti-Inflammatory Agents, Non-SteroidalAntioxidantsApoptosisCell LineCyclooxygenase 2Cyclooxygenase 2 InhibitorsCyclooxygenase InhibitorsDinoprostoneEnzyme InhibitorsIndolesKynuramineLipopolysaccharidesMacrophage ActivationMacrophagesMelatoninMiceNitric Oxide SynthaseNitric Oxide Synthase Type IINitritesProstaglandin AntagonistsProstaglandin-Endoperoxide SynthasesSuperoxides

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15975667

Citation

Mayo, Juan C., et al. "Anti-inflammatory Actions of Melatonin and Its Metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in Macrophages." Journal of Neuroimmunology, vol. 165, no. 1-2, 2005, pp. 139-49.
Mayo JC, Sainz RM, Tan DX, et al. Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. J Neuroimmunol. 2005;165(1-2):139-49.
Mayo, J. C., Sainz, R. M., Tan, D. X., Hardeland, R., Leon, J., Rodriguez, C., & Reiter, R. J. (2005). Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. Journal of Neuroimmunology, 165(1-2), 139-49.
Mayo JC, et al. Anti-inflammatory Actions of Melatonin and Its Metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in Macrophages. J Neuroimmunol. 2005;165(1-2):139-49. PubMed PMID: 15975667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. AU - Mayo,Juan C, AU - Sainz,Rosa M, AU - Tan,Dun-Xian, AU - Hardeland,Rüdiger, AU - Leon,Josefa, AU - Rodriguez,Carmen, AU - Reiter,Russel J, PY - 2005/04/29/received PY - 2005/05/04/accepted PY - 2005/6/25/pubmed PY - 2005/9/9/medline PY - 2005/6/25/entrez SP - 139 EP - 49 JF - Journal of neuroimmunology JO - J Neuroimmunol VL - 165 IS - 1-2 N2 - Inflammation is a complex phenomenon involving multiple cellular and molecular interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical role in the inflammatory response and its over-expression has been associated with several pathologies including neurodegenerative diseases and cancer. Melatonin is the main product of the pineal gland with well documented antioxidant and immuno-modulatory effects. Since the action of the indole on COX-2 has not been previously described, the goal of the present report was to test the effect of melatonin on the activities of COX-2 and inducible nitric oxide synthase (iNOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2 activation induced by LPS, without affecting COX-1 protein levels. The structurally related compound 6-methoxy-melatonin only partially prevented the increase in COX-2 protein levels induced by the toxin. Likewise melatonin prevented iNOS activation and reduced the concentration of products from both enzymes, PGE(2) and nitric oxide. Another endogenous antioxidant like N-acetyl-cysteine (NAC) did not reduced COX-2 significantly. The current finding corroborates a role of melatonin as an anti-inflammatory agent and, for the first time, COX-2 and iNOS as molecular targets for either melatonin or its metabolites AFMK and AMK. These anti-inflammatory actions seem not to be exclusively mediated by the free radical scavenging properties of melatonin. As a consequence, the present work suggests these substances as a new class of potential anti-inflammatory agents without the classical side effects due to COX-1 inhibition. SN - 0165-5728 UR - https://www.unboundmedicine.com/medline/citation/15975667/Anti_inflammatory_actions_of_melatonin_and_its_metabolites_N1_acetyl_N2_formyl_5_methoxykynuramine__AFMK__and_N1_acetyl_5_methoxykynuramine__AMK__in_macrophages_ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓79]

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