Immune-pineal axis: time-niology integrated to surveillance and defense

• Grant number: 13/13691-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: April 01, 2014
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Regina Pekelmann Markus
• Grantee: Regina Pekelmann Markus
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Anamaria Aranha Camargo ; Helena Bonciani Nader ; Lucile Maria Floeter-Winter ; Pedro Augusto Carlos Magno Fernandes ; Raphael Bessa Parmigiani ; Suely Kazue Nagahashi Marie ; Zulma Felisbina da Silva Ferreira
• Associated research grant(s): 14/20809-1 - Multiuser equipment approved in grant 2013/13691-1 - for acquisition of AMNIS flow-sight - Millipore, AP.EMU
• Associated scholarship(s): 15/04557-5 - The activation of immune-pineal axis by high-fat diet, BP.PD

Abstract

The Immune-Pineal Axis hypothesis provides the molecular basis for understanding the role of melatonin in the surveillance for external aggressions and internal disorganization of the [39, 97, 98]. In addition, it explains how the production of melatonin is shifted from the pineal gland to peripheral immune cells and microglias during an innate immune response. The goal of the present project is to translate cellular and molecular data to animal models, and clinical practice. The project is divided in three areas:1 - Molecular basis that coordinate the Immune-Pineal Axis (IPA),2 - Test of the IPA hypothesis in animal models of light inflammation (obesity and air pollution) and in models of parasitosis.3 - Clinical Application - we are initiating the project with gliomas, in order to predict the prognosis of the invisibility of the tumor, taking into account the level of melatonin in the primary glioma and will continue the studies linking the nocturnal melatonin surge to predictor indexes for the output in antidepressant therapy. (AU)

Scientific publications

(32)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARKUS, REGINA P.; FERNANDES, PEDRO A.; KINKER, GABRIELA S.; CRUZ-MACHADO, SANSERAY DA SILVEIRA; MARCOLA, MARINA. Immune-pineal axis - acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes. British Journal of Pharmacology, v. 175, n. 16, SI, p. 3239-3250, AUG 2018. (14/27287-0, 15/04557-5, 10/52687-1, 13/13691-1)

PIRES-LAPA, MARCO A.; CARVALHO-SOUSA, CLAUDIA E.; CECON, ERIKA; FERNANDES, PEDRO A.; MARKUS, REGINA P.. beta-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 8, AUG 2018. (09/17923-9, 13/13691-1)

TONON, ANDRE C.; PILZ, LUISA K.; MARKUS, REGINA P.; HIDALGO, MARIA PAZ; ELISABETSKY, ELAINE. Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies. FRONTIERS IN PSYCHIATRY, v. 12, APR 8 2021. (13/13691-1)

CARVALHO-SOUSA, CLAUDIA EMANUELE; PEREIRA, ELIANA P.; KINKER, GABRIELA S.; VERAS, MARIANA; FERREIRA, ZULMA S.; BARBOSA-NUNES, FERNANDA P.; MARTINS, JOILSON O.; SALDIVA, PAULO H. N.; REITER, RUSSEL J.; FERNANDES, PEDRO A.; et al. Immune-pineal axis protects rat lungs exposed to polluted air. Journal of Pineal Research, v. 68, n. 3, FEB 2020. (13/13691-1, 12/04508-6)

MONTEIRO TITON, STEFANNY CHRISTIE; TITON JUNIOR, BRAZ; ASSIS, VANIA REGINA; VASCONCELOS-TEIXEIRA, RONYELLE; GARCIA NETO, PATRICIO GETULIO; LIMA, ALAN SIQUEIRA; FERREIRA, LETICIA DE FRANCA; FERNANDES, PEDRO A.; GOMES, FERNANDO RIBEIRO; MARKUS, REGINA P.. Hormonal daily variation co-varies with immunity in captive male bullfrogs (Lithobates catesbeianus). General and Comparative Endocrinology, v. 303, MAR 1 2021. (14/16320-7, 13/13691-1)

BRAZACA, LAIS C.; BRAMORSKI, CAMILA B.; CANCINO-BERNARDI, JULIANA; CRUZ-MACHADO, SANSERAY DA SILVEIRA; MARKUS, REGINA P.; JANEGITZ, BRUNO C.; ZUCOLOTTO, VALTENCIR. An antibody-based platform for melatonin quantification. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 171, p. 94-100, NOV 1 2018. (13/13691-1, 15/02623-0, 15/19099-2)

CORDOBA-MORENO, MARLINA O.; SANTOS, GABRIELA CHRISTINE; MUXEL, SANDRA M.; DOS SANTOS-SILVA, DEBORA; QUILES, CAROLINE L.; SOUSA, KASSIANO D. S.; MARKUS, REGINA P.; FERNANDES, PEDRO AUGUSTO C. M.. IL-10-induced STAT3/NF-κB crosstalk modulates pineal and extra-pineal melatonin synthesis. Journal of Pineal Research, v. 76, n. 1, p. 23-pg., 2023-11-22. (10/52687-1, 12/23122-1, 13/13691-1)

KINKER, G. S.; OSTROWSKI, L. H.; RIBEIRO, P. A. C.; CHANOCH, R.; MUXEL, S. M.; TIROSH, I.; SPADONI, G.; RIVARA, S.; MARTINS, V. R.; SANTOS, T. G.; et al. MT1 and MT2 melatonin receptors play opposite roles in brain cancer progression. JOURNAL OF MOLECULAR MEDICINE-JMM, v. 99, n. 2, JAN 2021. (14/23830-1, 14/27287-0, 13/13691-1, 17/24287-8, 14/50943-1, 15/23348-8)

GARCIA NETO, PATRICIO G.; TITON, STEFANNY C. M.; ASSIS, VANIA R.; MUXEL, SANDRA M.; TITON JR, BRAZ; FERREIRA, LETICIA F.; MARKUS, REGINA P.; GOMES, FERNANDO R.; FERNANDES, PEDRO A. C. M.. Immune and endocrine responses of Cururu toads (Rhinella icterica) in their natural habitat after LPS stimulation. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, v. 269, p. 9-pg., 2022-04-15. (13/13691-1, 14/16320-7)

MACK, JOSIEL MILENO; MOURA, TAINARA DE MENEZES; BOBINSKI, FRANCIANE; MARTINS, DANIEL FERNANDES; CUNHA, RODRIGO A.; WALZ, ROGER; FERNANDES, PEDRO AUGUSTO; MARKUS, REGINA PEKELMANN; DAFRE, ALCIR LUIZ; PREDIGER, RUI DANIEL. Neuroprotective effects of melatonin against neurotoxicity induced by intranasal sodium dimethyldithiocarbamate administration in mice. NeuroToxicology, v. 80, p. 144-154, SEP 2020. (13/13691-1)

KINKER, G. S.; OSTROWSKI, L. H.; OBA-SHINJO, S. M.; MUXEL, S. M.; MARIE, S. K. N.; MARKUS, R. P.; FERNANDES, P. A.. THE PROGNOSTIC VALUE OF THE MELATONERGIC SYSTEM-BASED ASMT:CYP1B1 INDEX IN SOLID TUMORS. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v. 121, p. 1-pg., 2017-08-01. (14/27287-0, 10/52687-1, 13/13691-1)

JOCKERS, RALF; DELAGRANGE, PHILIPPE; DUBOCOVICH, MARGARITA L.; MARKUS, REGINA P.; RENAULT, NICOLAS; TOSINI, GIANLUCA; CECON, ERIKA; ZLOTOS, DARIUS P.. Update on melatonin receptors: IUPHAR Review 20. British Journal of Pharmacology, v. 173, n. 18, p. 2702-2725, SEP 2016. (13/13691-1)

KINKER, GABRIELA S.; OBA-SHINJO, SUELI M.; CARVALHO-SOUSA, CLAUDIA E.; MUXEL, SANDRA M.; MARIE, SUELY K. N.; MARKUS, REGINA P.; FERNANDES, PEDRO A.. Melatonergic system-based two-gene index is prognostic in human gliomas. Journal of Pineal Research, v. 60, n. 1, p. 84-94, JAN 2016. (13/13691-1, 10/52687-1)

CECON, ERIKA; CHEN, MIN; MARCOLA, MARINA; FERNANDES, PEDRO A. C.; JOCKERS, RALF; MARKUS, REGINA P.. Amyloid beta peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway. FASEB JOURNAL, v. 29, n. 6, p. 2566-2582, JUN 2015. (09/17923-9, 11/01304-8, 07/07871-6, 13/13691-1)

MARCOLA, MARINA; LOPES-RAMOS, CAMILA M.; PEREIRA, ELIANA P.; CECON, ERIKA; FERNANDES, PEDRO A.; TAMURA, EDUARDO K.; CAMARGO, ANAMARIA A.; PARMIGIANI, RAPHAEL B.; MARKUS, REGINA P.. Light/Dark Environmental Cycle Imposes a Daily Profile in the Expression of microRNAs in Rat CD133(+) Cells. Journal of Cellular Physiology, v. 231, n. 9, p. 1953-1963, SEP 2016. (13/13691-1, 09/17785-5, 09/17923-9, 12/04508-6, 11/01304-8)

CRUZ-MACHADO, SANSERAY DA SILVEIRA; TAMURA, EDUARDO K.; CARVALHO-SOUSA, CLAUDIA E.; ROCHA, VANDERLEI AMADEU; PINATO, LUCIANA; FERNANDES, PEDRO A. C.; MARKUS, REGINA P.. Daily corticosterone rhythm modulates pineal function through NF kappa B-related gene transcriptional program. SCIENTIFIC REPORTS, v. 7, MAY 18 2017. (07/07871-6, 13/13691-1)

MUXEL, SANDRA MARCIA; LARANJEIRA-SILVA, MARIA FERNANDA; CARVALHO-SOUSA, CLAUDIA EMANUELLE; FLOETER-WINTER, LUCILE MARIA; MARKUS, REGINA P.. The RelA/cRel nuclear factor-B (NF-B) dimer, crucial for inflammation resolution, mediates the transcription of the key enzyme in melatonin synthesis in RAW 264.7 macrophages. Journal of Pineal Research, v. 60, n. 4, p. 394-404, MAY 2016. (14/50717-1, 10/52688-8, 13/13691-1, 12/15263-4)

FERNANDES, PEDRO A.; TAMURA, EDUARDO K.; D'ARGENIO-GARCIA, LETICIA; MUXEL, SANDRA M.; CRUZ-MACHADO, SANSERAY DA SILVEIRA; MARCOLA, MARINA; CARVALHO-SOUSA, CLAUDIA E.; CECON, ERIKA; FERREIRA, ZULMA S.; MARKUS, REGINA P.. Dual Effect of Catecholamines and Corticosterone Crosstalk on Pineal Gland Melatonin Synthesis. Neuroendocrinology, v. 104, n. 2, p. 126-134, 2017. (13/13691-1, 10/52687-1)

BARBOSA LIMA, LEILA ELIZA; MUXEL, SANDRA MARCIA; KINKER, GABRIELA S.; CARVALHO-SOUSA, CLAUDIA EMANUELE; CRUZ-MACHADO, SANSERAY DA SILVEIRA; MARKUS, REGINA P.; CARLOS MAGNO FERNANDES, PEDRO AUGUSTO. STAT1-NF kappa B crosstalk triggered by interferon gamma regulates noradrenaline-induced pineal hormonal production. Journal of Pineal Research, v. 67, n. 3, OCT 2019. (12/09622-1, 10/52687-1, 13/13691-1)

LARANJEIRA-SILVA, MARIA FERNANDA; ZAMPIERI, RICARDO A.; MUXEL, SANDRA M.; FLOETER-WINTER, LUCILE MARIA; MARKUS, REGINA P.. Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism. Journal of Pineal Research, v. 59, n. 4, p. 478-487, NOV 2015. (10/52688-8, 13/13691-1)

SOUZA-TEODORO, LUIS HENRIQUE; DARGENIO-GARCIA, LETICIA; PETRILLI-LAPA, CAMILA LOPES; SOUZA, EWERTON DA SILVA; FERNANDES, PEDRO A. C. M.; MARKUS, REGINA P.; FERREIRA, ZULMA S.. Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland. Journal of Pineal Research, v. 60, n. 2, p. 242-249, MAR 2016. (12/06110-0, 07/07871-6, 13/13691-1, 09/12307-8)

FERREIRA, ZULMA. The multi-faceted role of ATP in the control of melatonin synthesis - New insights for onset and progression of diseases. PURINERGIC SIGNALLING, v. 14, p. 1-pg., 2018-12-01. (13/13691-1, 12/06110-0, 11/12649-6, 09/12307-8)

MARKUS, REGINA P.; FERNANDES, PEDRO A.; KINKER, GABRIELA S.; CRUZ-MACHADO, SANSERAY DA SILVEIRA; MARCOLA, MARINA. Immune-pineal axis - acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes. British Journal of Pharmacology, v. 175, n. 16, p. 12-pg., 2018-08-01. (14/27287-0, 15/04557-5, 10/52687-1, 13/13691-1)

PIRES-LAPA, MARCO A.; CARVALHO-SOUSA, CLAUDIA E.; CECON, ERIKA; FERNANDES, PEDRO A.; MARKUS, REGINA P.. beta-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 8, p. 13-pg., 2018-08-01. (09/17923-9, 13/13691-1)

FREITAS, JULIANA JURY; XAVIER, NICOLI BERTUOL; TONON, ANDRE COMIRAN; CARISSIMI, ALICIA; PIZUTTI, LEANDRO TIMM; VIEIRA ILGENFRITZ, CARLOS AUGUSTO; MARKUS, REGINA PEKELMANN; HIDALGO, MARIA PAZ. 6-Sulfatoxymelatonin predicts treatment response to fluoxetine in major depressive disorder. THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY, v. 9, DEC 2019. (13/13691-1)

PINATO, LUCIANA; GALINA SPILLA, CAIO SERGIO; MARKUS, REGINA PEKELMANN; CRUZ-MACHADO, SANSERAY DA SILVEIRA. Dysregulation of Circadian Rhythms in Autism Spectrum Disorders. CURRENT PHARMACEUTICAL DESIGN, v. 25, n. 41, p. 4379-4393, 2019. (11/51495-4, 13/13691-1)

KOMEGAE, EVILIN N.; FONSECA, MONIQUE T.; CRUZ-MACHADO, SANSERAY DA SILVEIRA; TURATO, WALTER M.; FILGUEIRAS, LUCIANO R.; MARKUS, REGINA P.; STEINER, ALEXANDRE A.. Site-Specific Reprogramming of Macrophage Responsiveness to Bacterial Lipopolysaccharide in Obesity. FRONTIERS IN IMMUNOLOGY, v. 10, JUN 28 2019. (12/03831-8, 18/03418-0, 14/03719-9, 13/13691-1, 15/04557-5, 16/04921-1, 17/13350-0, 14/17407-9)

OLIVEIRA BASTOS, PRISCILLA RACHEL; MONTEIRO TITON, STEFANNY CHRISTIE; TITON JUNIOR, BRAZ; GOMES, FERNANDO RIBEIRO; MARKUS, REGINA P.; FERREIRA, ZULMA S.. Daily and LPS-induced variation of endocrine mediators in cururu toads (Rhinella icterica). CHRONOBIOLOGY INTERNATIONAL, v. 39, n. 1, SEP 2021. (13/13691-1, 13/00900-1)

TITON JUNIOR, BRAZ; TITON, STEFANNY CHRISTIE MONTEIRO; ASSIS, VANIA REGINA; BARSOTTI, ADRIANA MARIA GIORGI; VASCONCELOS-TEIXEIRA, RONYELLE; FERNANDES, PEDRO AUGUSTO CARLOS MAGNO; GOMES, FERNANDO RIBEIRO. LPS-induced immunomodulation and hormonal variation over time in toads. JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY, v. 335, n. 6, p. 541-551, JUL 2021. (16/01782-0, 13/13691-1, 15/23801-4, 14/16320-7)

CORDOBA-MORENO, MARLINA O.; MENDES, MARIANA TRIVILIN; MARKUS, REGINA P.; FERNANDES, PEDRO AUGUSTO. Rat resistance to rheumatoid arthritis induction as a function of the early-phase adrenal-pineal crosstalk. JOURNAL OF PHYSIOLOGY-LONDON, v. 601, n. 3, p. 15-pg., 2022-12-08. (10/52687-1, 13/13691-1)

MONTEIRO TITON, STEFANNY CHRISTIE; ASSIS, VANIA REGINA; TITON JUNIOR, BRAZ; KINKER, GABRIELA SARTI; TEIXEIRA DE QUEIROZ HAZARBASSANOV, NICOLLE GILDA; LIMA, ALAN SIQUEIRA; MASSOCO, CRISTINA DE OLIVEIRA; FERNANDES, PEDRO A.; GOMES, FERNANDO RIBEIRO; MARKUS, REGINA P.. Optimizing studies of phagocytic activity by flowsight cytometry in amphibians. South American Journal of Herpetology, v. 23, n. 1, p. 9-pg., 2022-04-01. (13/00900-1, 14/16320-7, 13/13691-1)

CORDOBA-MORENO, MARLINA O.; DE SOUZA, EWERTON DA SILVA; QUILES, CAROLINE L.; DOS SANTOS-SILVA, DEBORA; KINKER, GABRIELA S.; MUXEL, SANDRA M.; MARKUS, REGINA P.; FERNANDES, PEDRO A.. Rhythmic expression of the melatonergic biosynthetic pathway and its differential modulation in vitro by LPS and IL10 in bone marrow and spleen. SCIENTIFIC REPORTS, v. 10, n. 1, MAR 16 2020. (13/13691-1, 15/23348-8)