| Grant number: | 12/04508-6 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | May 01, 2012 |
| Effective date (End): | April 30, 2015 |
| Field of knowledge: | Biological Sciences - Pharmacology - General Pharmacology |
| Principal researcher: | Regina Pekelmann Markus |
| Grantee: | Eliana Paula Pereira |
| Home Institution: | Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 07/07871-6 - Imune-pineal Axis: injury shifts melatonin production from endocrine to paracrine, AP.TEM |
Abstract Melatonin, a hormone released from the pineal gland during the night the light / dark cycle environment, acts as a cytoprotective agent and immunomodulator, regardless of time of day. Our working group found that not only the hormone melatonin which is involved in the defense system, the pineal gland itself participates in this action in a two-way conversation with the immune system. Furthermore, melatonin has been shown in vitro to reduce the expression of adhesion molecules, enzyme-induced nitric oxide synthase (iNOS) and nuclear translocation of transcription factor kappa B (NFKB) of endothelial cells. These events may result in the effect of melatonin on the reduction of rolling, adhesion and migration of leukocytes as observed in vivo.Melatonin produced by the pineal gland acts as a brake on the assembly of the inflammatory response in the dark phase. The proinflammatory cytokines or pathogen-associated molecular pattern (PAMP's) activate receptors located in the pineal gland preventing the production of melatonin nocturnal thereby facilitating the assembly of an inflammatory response. Processes that may suppress nocturnal melatonin production, although important for the protection of the organism, will certainly make a man more susceptible to diseases resulting from inflammatory responses spurious.Air pollution is a major risk factor for urban populations with deleterious effects on health and increased morbidity and mortality. This material is formed by various physical states and various chemical natures: gas, liquid and particulate matter (PM). The demonstration that this material interacts with the same receptors that PAMP's opens the perspective that pollution may facilitate the mounting of inflammatory responses.The objective of this project is to investigate whether environmental pollution interferes with the atmospheric reactivity of endothelial cells and whether these changes are a result of variations in plasma concentrations of melatonin. Studies will be made functional and molecular level by evaluating the expression of adhesion molecules, enzymes and the transduction pathways involved in the inflammatory response.In summary, this project aims to base the investigation of pharmacological actions to protect or even reverse the harmful effects of air pollution generated through knowledge of the immune-pineal axis, and if possible using melatonin or its analogues as therapeutic agents. | |
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