The time-course of the innate immunological response involves a pro-inflammatory phase followed by an anti-inflammatory phase. Pro-inflammatory responses are defense reaction against several stressor conditions. They are followed by an anti-inflammatory phase which avoid exacerbation or chronification of the inflammation. Recently we have shown that the pineal gland is a player in the bidirectional control of the inflammatory response. Healthy organisms stay in stand-by mode, ready to react. The nocturnal melatonin surge impairs the rolling and adherance of leukocytes to endothelial layers, limiting cell migration, and stimulates nocturnal production of IL-2 by T helper lymphocytes, exerting an immunostimulatory effect. Otherwise, the release of TNF-alpha; from activated macrophages suppresses the nocturnal melatonin surge, allowing a full cell migration and inhibiting IL-2 production. In sequence, activated mononuclear and polymorphonuclear cells produce melatonin in a paracrine manner at the site of injury, which scavenges free radicals and collaborates to resolve the inflammatory response. The sequential diminution of TNFá production is followed by the recovery of the nocturnal melatonin surge and IL-2 production. In summary, the immune-pineal axis, implicated in the sequential involvement of the melatonin produced by the pineal gland and immune-competent cells, is an integral participant of the innate immune response. The present project was designed to determine the cellular and molecular mechanisms involved in the control of pineal and extra-pineal melatonin by pro- and anti-inflammatory mediator, as to extend if other forms of injury, such as psychological stress may also impairs pineal melatonin production, interfering therefore in the transduction of the light/dark cycle to the whole body. We also will increase our clinical observations providing new paradigm for testing the immune-pineal axis. Therefore, this project intend to establish the molecular, cellular and organismic conditions for a shuttle between endocrine and paracrine production of melatonin. (AU)
Articles published in Pesquisa FAPESP Magazine about the research grant:
CRUZ-MACHADO, SANSERAY DA SILVEIRA;
CARVALHO-SOUSA, CLAUDIA EMANUELE;
TAMURA, EDUARDO KOJI;
MAGNO FERNANDES, PEDRO AUGUSTO CARLOS;
WERNECK DE AVELLAR, MARIA CHRISTINA;
FERREIRA, ZULMA SILVA;
MARKUS, REGINA PEKELMANN.
TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway.
Journal of Pineal Research,
Web of Science Citations: 61.