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| Author(s): |
Marina Marçola
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) |
| Defense date: | 2011-06-14 |
| Examining board members: |
Regina Pekelmann Markus;
Catarina de Fatima Pereira Teixeira;
Lucile Maria Floeter Winter
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| Advisor: | Regina Pekelmann Markus |
| Abstract | |
The endothelium is the vascular internal cellular layer, responsible for vascular homeostasis. Additionally, it regulates immune cells entrance during an inflammatory response. The endothelial layer is the focus of many studies due to its facility of culture expansion, but its biology is not yet totally understood. Because of its privileged localization, the endothelium is susceptible to plasma compounds changes. Melatonin, rhythmically produced by pineal gland and in a non rhythm way in others tissues, has citoprotector properties. Many studies have already shown that melatonin acts on endothelium as an anti-inflammatory mediator, through different mechanisms of action and concentrations ranges. Considering our work hypothesis, the immune-pineal axis, that suggests that the pineal gland and immune system are integrated through a bidirectional communication, melatonin rhythm production is inhibited during an injury, permitting the mounting of immune response independently of the hour of the day. This dissertation is based on the hypothesis that endothelial cells presents a rhythm in its machinery that alters the response intensity due to an inflammatory stimuli. We analyzed how LPS systemic treatment affects the melatonin nocturnal production, modulating the endothelial cells reactivity of microcirculation. We demonstrated that LPS treatment reduced plasma melatonin level and inhibited gene transcription of key enzyme, AA-NAT. On the periphery, LPS treatment increased endothelial cells reactivity independently of the hour of the day even after 18 days in culture. This effect was transient, once the parameters analyzed returned to basal levels when the treatment was done six hours before the death. Melatonin administrated together with LPS, reverted LPS effects on the endothelial cells, and also reduced plasma TNF concentration. Endothelial cells obtained from animal killed at nighttime are more activated than cells obtained from animals killed at daytime. Generally, the endothelial cells effects are inversely correlated with plasma melatonin level. These data suggests that endothelial cells have a \"cellular memory\", because they are capable to retain the information of donor animal state even after all culture proceedings. Additionally, we demonstrated the immune-pineal axis dynamics in vivo. All together, our results permit to conclude that melatonin primes the endothelial cells, modulating their reactivity according to the hour of the day and donor animal health. (AU) | |
| FAPESP's process: | 09/04000-0 - Effect of the Hour of the Day on the Reactivity of Primary Cultures of Endothelial Cells |
| Grantee: | Marina Marçola Pereira de Freitas |
| Support Opportunities: | Scholarships in Brazil - Master |