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A review of the molecular aspects of melatonin’s anti‐inflammatory actions: recent insights and new perspectives
Author(s) -
Mauriz José L.,
Collado Pilar S.,
Veneroso Christiano,
Reiter Russel J.,
GonzálezGallego Javier
Publication year - 2013
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2012.01014.x
Subject(s) - melatonin , transcription factor , signal transduction , microbiology and biotechnology , biology , chemokine , nitric oxide synthase , inflammation , pineal gland , kinase , nitric oxide , cell signaling , immunology , biochemistry , endocrinology , gene
Abstract: Melatonin is a highly evolutionary conserved endogenous molecule that is mainly produced by the pineal gland, but also by other nonendocrine organs, of most mammals including man. In the recent years, a variety of anti‐inflammatory and antioxidant effects have been observed when melatonin is applied exogenously under both in vivo and in vitro conditions. A number of studies suggest that this indole may exert its anti‐inflammatory effects through the regulation of different molecular pathways. It has been documented that melatonin inhibits the expression of the isoforms of inducible nitric oxide synthase and cyclooxygenase and limits the production of excessive amounts of nitric oxide, prostanoids, and leukotrienes, as well as other mediators of the inflammatory process such as cytokines, chemokines, and adhesion molecules. Melatonin’s anti‐inflammatory effects are related to the modulation of a number of transcription factors such as nuclear factor kappa B, hypoxia‐inducible factor, nuclear factor erythroid 2‐related factor 2, and others. Melatonin’s effects on the DNA‐binding capacity of transcription factors may be regulated through the inhibition of protein kinases involved in signal transduction, such as mitogen‐activated protein kinases. This review summarizes recent research data focusing on the modulation of the expression of different inflammatory mediators by melatonin and the effects on cell signaling pathways responsible for the indole’s anti‐inflammatory activity. Although there are a numerous published reports that have analyzed melatonin’s anti‐inflammatory properties, further studies are necessary to elucidate its complex regulatory mechanisms in different cellular types and tissues.