Regina P. Markus

• Full Professor
• Principal Investigator at University of São Paulo

Introduction The reproductive system is tightly regulated by environmental and physiological signals. Melatonin, known as the hormone of darkness, plays a crucial role in regulating both the circadian and reproductive systems in mammals. Hypothyroidism is a key endocrine disorder that harms the reproductive system. Despite many studies on melatonin...

In mammal’s pineal glands, ATP interacts with the high-affinity P2Y1 and the low-affinity P2X7 receptors. ATP released from sympathetic nerve terminals potentiates noradrenaline-induced serotonin N-acetyltransferase (Snat) transcription, N-acetylserotonin (NAS), and melatonin (MLT) synthesis. Circulating melatonin impairs the expression of adhesion...

Synopsis Melatonin is a hormone known as an endogenous temporal marker signaling the dark phase of the day. Although the eyes seem to be the main site of melatonin production in amphibians, little information is available about the natural variation in ocular melatonin levels and its modulation following immune stimulation. We investigated the dail...

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is s...

Saliva measurements serve as a noninvasive tool for clinically monitoring newborns (NB) and children, a vulnerable population with promising potential for both research and clinical practice. Saliva acts as a repository for various inflammatory biomarkers involved in diverse biological functions. Particularly for children, it offers numerous advant...

Immune‐pineal axis activation is part of the assembly of immune responses. Proinflammatory cytokines inhibit the pineal synthesis of melatonin while inducing it in macrophages by mechanisms dependent on nuclear factor‐κB (NF‐κB) activation. Cytokines activating the Janus kinase/signal transducer and activator of transcription (STAT) pathways, such...

Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [40]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon.

Chronic inflammatory diseases are triggered by causal stimuli that might occur long before the appearance of the symptoms. Increasing evidence suggests that these stimuli are necessary but not always sufficient to induce the diseases. The murine model of type II collagen emulsified in Freund's incomplete adjuvant (collagen‐induced arthritis) to ind...

Background Alterations in circadian system organization have been related to major depressive disorder manifestations. This study aimed to evaluate chronobiological parameters, such as sleep, levels of 6-sulfatoxymelatonin, and others derived from actimetry as potential predictors of adequate treatment response in MDD. Methods 98 adult women with...

Melatonin synthesis by extrapineal sources adjusts physiological and pathophysiological processes in several types of cells and tissues. As measuring locally produced melatonin in fresh tissues might be a challenge due to limited material availability, we created a simple predictive model, the MEL-Index, which infers the content of tissue melatonin...

The pineal gland is a key player in surveillance and defense responses. In healthy conditions, nocturnal circulating melatonin (MEL) impairs the rolling and adhesion of leukocytes to the endothelial layer. Fungi, bacteria, and pro-inflammatory cytokines block nocturnal pineal MEL synthesis, facilitating leukocyte migration to injured areas. ATP is...

Neuroimunomodulação — Interações Imunoneuroendócrinas na Saúde e na Doença surge sob o patrocínio do Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação – INCT/NIM. Sua equipe autoral congrega pesquisadores da Fundação Oswaldo Cruz, Rio de Janeiro, e da Universidade Federal do Rio Grande do Sul – UFRGS. Estuda os fenômenos biológicos...

Phagocytosis is a primary and highly conserved mechanism for clearing the extracellular milieu from pathogens and debris. In amphibians, the lack of antibodies for characterizing the different phenotypes of phagocytic cells has impaired the study of the phagocytic process. We used conventional and flowsight cytometry to determine immune cells' phag...

Glucocorticoids and melatonin display immunomodulatory functions, with both immune-stimulatory and suppressor effects, depending on the context. While their immune properties are well-explored in mammals, there are still few studies on this immune-endocrine interaction in an inflammatory context in amphibians, all of them under captivity conditions...

Microglia, the sentinels of the central nervous system, are responsible for the surveillance and the innate defense against pathogen or danger/damage-associated molecular patterns. The response is fine-tuned to restrain pro-inflammatory responses, preserving neighboring cells. At the injured area, microglia temporarily shift to a pro-inflammatory p...

Melatonin is a highly conserved molecule found in prokaryotes and eukaryotes that acts as the darkness hormone, translating environmental lighting to the whole body, and as a moderator of innate and acquired defense, migration, and cell proliferation processes. This review evaluates the importance of pineal activity in monitoring PAMPs and DAMPs an...

Increased plasma glucocorticoids (corticosterone – CORT, in amphibians) and melatonin (MEL) are associated with the daily activity phase and with environmental darkness, respectively. Besides, CORT and MEL also play pivotal immunomodulatory roles in several vertebrates. Herein we described the daily profile of plasma MEL and CORT for Rhinella icter...

Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [40]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon.

Daily rhythm of melatonin synchronizes the body to the light/dark environmental cycle. Several hypotheses have been raised to understand the intersections between melatonin and depression, in which changes in rest-activity and sleep patterns are prominent. This review describes key experimental and clinical evidence that link melatonin with the eti...

Primary brain tumors remain among the deadliest of all cancers. Glioma grade IV (glioblastoma), the most common and malignant type of brain cancer, is associated with a 5-year survival rate of < 5%. Melatonin has been widely reported as an anticancer molecule, and we have recently demonstrated that the ability of gliomas to synthesize and accumulat...

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of Autism Spectrum Disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6‐sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin‐6 (IL‐6) in 20 controls and 20 ASD participant...

The pandemic dissemination of the SARS-CoV-2 led, on the one hand, to a worldwide effort to develop mechanistic-based therapeutics and vaccines, and on the other hand, the searching for determining the spreaders and the mechanisms of transmission. Melatonin, a multitask molecule, orchestrates defense responses by allowing the proper mounting, durat...

Almost all physiological processes within the organism, including immune parameters and hormones, follow a circadian rhythm. These daily fluctuations are often observed in free-living organisms; however, little is known regarding hormonal and immune daily variations in anurans, particularly under laboratory conditions. This study aimed to investiga...

Exposure to fungicide ziram (zinc dimethyldithiocarbamate) has been associated with increased incidence of Parkinson’s disease (PD). We recently demonstrated that the intranasal (i.n.) administration of sodium dimethyldithiocarbamate (NaDMDC, a more soluble salt than ziram) induces PD-like behavioral and neurochemical alterations in mice. We now in...

Daily oscillation of the immune system follows the central biological clock outputs control such as melatonin produced by the pineal gland. Despite the literature showing that melatonin is also synthesized by macrophages and T lymphocytes, no information is available regarding the temporal profile of the melatonergic system of immune cells and orga...

Inflammatory joint conditions are characterized by synovial inflammation, which involves activation of fibroblast-like synoviocytes (FLSs) and production of inflammatory mediators and matrix metalloproteases (MMPs) in joints. This study showed that the snake venom metalloprotease (SVMP) BaP1 activates FLSs to produce PGE2 by a mechanism dependent o...

Environmental pollution in the form of particulate matter <2.5 μm (PM2.5) is a major risk factor for diseases such as lung cancer, chronic respiratory infections and major cardiovascular diseases. Our goal was to show that PM2.5, eliciting a proinflammatory response activates the immune‐pineal axis, reducing the pineal synthesis and increasing the...

Almost all physiological processes within the organism, including immune parameters and hormones, follow a circadian rhythm. These 24h-day fluctuations are often observed in free-living organisms. However, in anurans, little is known regarding hormonal and immune daily variations, particularly under captive bred conditions. The aim of this study wa...

Background To date, no biomarker has been able to predict antidepressant response at an early blockade of norepinephrine or serotonin uptake. The transient nocturnal increase in plasma melatonin levels is upregulated by blocking these uptakes. The aim of this study was to test whether fluoxetine increase in urinary 6-sulfatoxymelatonin (aMT6s) is a...

Background The alterations in neurological and neuroendocrine functions observed in the autism spectrum disorder (ASD) involves environmentally dependent dysregulation of neurodevelopment, in interaction with multiple coding gene defects. Disturbed sleep-wake patterns, as well as abnormal melatonin and glucocorticoid secretion, show the relevance o...

Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [36]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon.

Hematopoietic stem and progenitor cells (HSPCs) are essential for daily mature blood cell production, host immunity, and osteoclast-mediated bone turnover. The timing at which stem cells give rise to mature blood and immune cells while maintaining the bone marrow (BM) reservoir of undifferentiated HSPCs and how these opposite tasks are synchronized...

Melatonin production by pineal glands is modulated by several immune signals. The nuclear translocation of nuclear factor kappa‐B (NFκB) homodimers, lacking transactivation domains, once induced by lipopolysaccharide (LPS) or tumor necrosis factor (TNF), inhibits the expression of Aanat gene and the synthesis of noradrenaline (NA)‐induced melatonin...

A fagocitose é um processo básico e altamente conservado entre os vertebrados, sendo responsável pela eliminação de debris extracelulares e de patógenos. Para avaliar individualmente cada tipo celular, bem como os mecanismos específicos associados ao processo de fagocitose, é necessário o uso de ferramentas específicas para caracterização das célul...

The mechanisms by which obesity may alter immune responses to pathogens are poorly understood. The present study assessed whether the intrinsic responsiveness of resident macrophages to bacterial lipopolysaccharide (LPS) is reprogrammed in high-fat diet (HFD)-induced obesity. Macrophages from adipose tissue, lung alveoli, and the peritoneal cavity...

Phosphoinositide signaling pathway orchestrates primordial molecular and cellular functions in both healthy and pathologic conditions. Phosphatidylinositol-5-phosphate 4-kinase type 2 lipid kinase (PIP4K2) family, which compromises PIP4K2A, PIP4K2B and PIP4K2C, has drawn the attention in human cancers. Particularly in hematological malignancies, PI...

Leishmaniases are neglected diseases that cause a large spectrum of clinical manifestations, from cutaneous to visceral lesions. The initial steps of the inflammatory response involve the phagocytosis of Leishmania and the parasite replication inside the macrophage phagolysosome. Melatonin, the darkness-signaling hormone, is involved in modulation...

Leishmania infectivity in melatonin-treated macrophages. BALB/c macrophages (2 × 105 cells) were pre-incubated for 1, 2, or 4 h with medium (untreated, white bar), vehicle (ethanol 0.0005%, gray bar), or 3 (blue bar) or 30 (light blue bar) nM of melatonin. After, macrophages were infected with L. amazonensis (MOI 5:1) and analyzed after 4 and 24 h....

Predicted mRNA-targets for miR-30e. The miRNA-mRNA interaction was predicted using miRecord tools (http://c1.accurascience.com/miRecords/) based in the integration of various prediction tools: DIANA-microT, MicroInspector, miRanda, MirTarget2, miTarget, NBmiRTar, PicTar, PITA, RNA22, RNAhybrid, and TargetScan/TargertScanS.

Predicted mRNA-targets for miR-495. The miRNA-mRNA interaction was predicted using miRecord tools (http://c1.accurascience.com/miRecords/) based in the integration of various prediction tools: DIANA-microT, MicroInspector, miRanda, MirTarget2, miTarget, NBmiRTar, PicTar, PITA, RNA22, RNAhybrid, and TargetScan/TargertScanS.

Predicted mRNA-targets for miR-721. The miRNA-mRNA interaction was predicted using miRecord tools (http://c1.accurascience.com/miRecords/) based in the integration of various prediction tools: DIANA-microT, MicroInspector, miRanda, MirTarget2, miTarget, NBmiRTar, PicTar, PITA, RNA22, RNAhybrid, and TargetScan/TargertScanS.

miRNAs Up-Down Regulation in melatonin and infected L. amazonensis infected macrophages compared to uninfected. The relative up- and down-regulation of miRNAs, expressed as boundaries of 1.5 and −1.5 of Fold Regulation, respectively. p < 0.05 was considered statistically significant. p-value was determined based on two-tailed Student's t-test. The...

Predicted mRNA-targets for miR-181c. The miRNA-mRNA interaction was predicted using miRecord tools (http://c1.accurascience.com/miRecords/) based in the integration of various prediction tools: DIANA-microT, MicroInspector, miRanda, MirTarget2, miTarget, NBmiRTar, PicTar, PITA, RNA22, RNAhybrid, and TargetScan/TargertScanS.

Predicted mRNA-targets for miR-694. The miRNA-mRNA interaction was predicted using miRecord tools (http://c1.accurascience.com/miRecords/) based in the integration of various prediction tools: DIANA-microT, MicroInspector, miRanda, MirTarget2, miTarget, NBmiRTar, PicTar, PITA, RNA22, RNAhybrid, and TargetScan/TargertScanS.

Bone marrow (BM) residing hematopoietic stem and progenitor cells (HSPC) replenish the blood with mature cells with a finite life span on a daily basis while maintaining the reservoir of undifferentiated stem cells. We recently showed that light/darkness onset induce two different BM HSPC peaks. Morning-induced norepinephrine and TNF secretion meta...

Shift work is unavoidable in modern societies, but at the same time disrupts biological rhythms and contributes to social distress and disturbance of sleep, health and well-being of shift workers. Shift work has been associated with some chronic diseases in which a chronic inflammatory condition may play a role. However, few studies investigating t...

Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin levels in the placenta and maternal...

Hematopoietic stem and progenitor cells (HSPCs) tightly couple maintenance of the bone marrow (BM) reservoir, including undifferentiated long-term repopulating hematopoietic stem cells (LT-HSCs), with intensive daily production of mature leukocytes and blood replenishment. We found two daily peaks of BM HSPC activity that are initiated by onset of...

Melatonin (5-methoxy-N-acetylserotonin), the pineal hormone, is also synthesized by immune-competent cells. The pineal hormone signals darkness, while melatonin synthesized on demand by activated macrophages at any hour of the day acts locally, favoring regulatory/tolerant phenotypes. Activation of β-adrenoceptors in pinealocytes is the main route...

Melatonin, the 'chemical signal of darkness', is responsible to regulate biological rhythms and different physiological processes. It is mainly produced by the pineal gland as a hormone in a rhythmic daily basis, but it may also be synthesized by other tissues, such as immune cells, under inflammatory conditions. Its abnormal circulating levels hav...

IntroductionMelanoma is the most lethal type of skin cancer, with increasing incidence and mortality rates worldwide. Multiple studies have demonstrated a link between cancer development/progression and circadian disruption; however, the complex role of tumor-autonomous molecular clocks remains poorly understood. With that in mind, we investigated...

O avanço da ciência, e sua relação com a formação de pessoal altamente qualificado na pós-graduação, geram pressões por desempenho e, em paralelo, dilemas éticos e conflitos de interesse entre os diversos atores envolvidos. A situação urge reflexões sobre quais são tais conflitos e como tratá-los, de forma a que sejam compatíveis com a formação de...

Melatonin is well known for its circadian production by the pineal gland, and there is a growing body of data showing that it is also produced by many other cells and organs, including immune cells. The chronobiotic role of pineal melatonin, as well as its protective effects in vitro and in vivo , have been extensively explored. However, the intera...

Melatonin and glucocorticoids are key hormones in determining daily rhythmicity and modulating defense responses. In nocturnal animals, corticosterone peaks at light/dark transition,while melatonin peaks at the middle of the night in both nocturnal and diurnal animals. The crosstalk between adrenal and pineal glands under inflammatory conditions in...

How bone marrow (BM) stem cells replenish the blood with mature cells while maintaining the reservoir of undifferentiated stem cells, is poorly understood. We report that murine leukocyte production and BM stem cell maintenance are regulated by light and darkness cues. We identified two daily peaks of BM stem and progenitor cell (HSPC) proliferatio...

The hippocampus is a brain region that is rich in nicotinic acetylcholine receptors (nAChRs), especially the α7 subtype. The hippocampus is severely affected in disorders that have a neuroinflammatory component, such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Previous studies demonstrated both in vivo and in vitro that nicotine...

Melatonin is synthesized by several tissues besides the pineal gland, and beyond its regulatory effects in light-dark cycle, melatonin is a hormone with neuroprotective, anti-inflammatory, and antioxidant properties. Melatonin acts as a free-radical scavenger, reducing reactive species and improving mitochondrial homeostasis. Melatonin also regulat...

Melatonin receptors are seven transmembrane-spanning proteins belonging to the G protein-coupled receptor super-family. In mammals, two melatonin receptor subtypes exit MT1 and MT2 encoded by the MTNR1A and MTNR1B genes, respectively. The current review provides an update on melatonin receptors by the corresponding sub-committee of the Internationa...

Morning shift sleep restriction has been associated with higher plasma IL-6 levels. The aim of this study was to investigate the effect of sleep duration on salivary IL-6. Sleep duration of morning shift workers was estimated by actigraphy. Workers with "longer sleep duration" (LSD; N = 6) and "shorter sleep duration" (SSD; N = 15) were then compar...

Background/aim: The nocturnal production of melatonin by the pineal gland is triggered by sympathetic activation of adrenoceptors and may be modulated by immunological signals. The effect of glucocorticoids on nocturnal melatonin synthesis is controversial, both stimulatory and inhibitory effects have been reported. During pathophysiological proce...

Lipopolysaccharide (LPS) modulates the transcription of the gene that codifies the enzyme arylalkylamine-N-acetyltransferase (AA-NAT) through nuclear translocation of the transcription factor nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB). AA-NAT converts serotonin to N-acetylserotonin, the ultimate precursor of melatonin. Activ...

Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransf...

The phenotype of primary cells in culture varies according to the donor environmental condition. We recently showed that the time of the day imposes a molecular program linked to the inflammatory response that is heritable in culture. Here we investigated whether microRNAs (miRNAs) would show differential expression according to the time when cells...

Gliomas, the most common primary brain tumors in adults, are classified into four malignancy grades according to morphological features. Recent studies have shown that melatonin treatment induces cytotoxicity in glioma-initiating cells and reduces the invasion and migration of glioma cell lines, inhibiting the nuclear factor κB (NFκB) oncopathway....

Acute inflammatory responses induced by bacteria or fungi block nocturnal melatonin synthesis by rodent pineal glands. Here, we show Leishmania infection does not impair daily melatonin rhythm in hamsters. Remarkably, the attenuated parasite burden and lesion progression in hamsters infected at nighttime was impaired by blockage of melatonin recept...

The suprachiasmatic nucleus (SCN) drives circadian rhythms in behavioral and physiological variables, including the inflammatory response. Shift work is known to disturb circadian rhythms and is associated with increased susceptibility to develop disease. In rodents, circadian disruption due to shifted light schedules (jet lag) induced increased in...

Melatonin is the hormone produced by the pineal gland known to regulate physiologic rhythms and to display immunomodulatory and neuroprotective properties. It has been reported that Alzheimer disease patients show impaired melatonin production and altered expression of the 2 G protein-coupled melatonin receptors (MTRs), MT1 and MT2, but the underly...

There is currently an urgent need for a viable, cheap, and readily available treatment for the Ebola virus outbreak in West Africa. Here, it is proposed that melatonin may have significant utility in helping the management of this outbreak. Optimizing natural killer (NK) cell responses seems crucial to surviving Ebola virus infection. Melatonin inc...

The constitutive activation of nuclear factor-κB (NF-κB), a key transcription factor involved in neuroinflammation, is essential for the survival of neurons in situ and of cerebellar granule cells in culture. Melatonin is known to inhibit the activation of NF-κB and has a cytoprotective function. In this study, we evaluated whether the cytoprotecti...

Although melatonin is mainly produced by the pineal gland, an increasing number of extra-pineal sites of melatonin synthesis have been described. We previously demonstrated the existence of bidirectional communication between the pineal gland and the immune system that drives a switch in melatonin production from the pineal gland to peripheral orga...

Background: Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modul...

Pineal gland melatonin is the darkness hormone, while extra-pineal melatonin produced by the gonads, gut, retina, and immune competent cells acts as a paracrine or autocrine mediator. The well-known immunomodulatory effect of melatonin is observed either as an endocrine, a paracrine or an autocrine response. In mammals, nuclear translocation of nuc...

Many cells in the organism besides pinealocytes, synthesize melatonin. Here, we evaluate both the mechanism of zymosan-induced melatonin synthesis and its autocrine effect in human colostral mononuclear cells. The synthesis of melatonin was induced by activation of the transcription factor nuclear factor kappa B (NF-κB), as either the blockade of t...

Objective: Activation of the immune-pineal axis induces a transient reduction in nocturnal melatonin in the plasma during the proinflammatory phase of an innate immune response to allow the proper migration of leukocytes to the lesion site. This transient reduction should be regulated by inflammatory mediators, which are responsible for the fine-t...

We demonstrate that during inflammatory responses the nuclear factor kappa B (NF-κB) induces the synthesis of melatonin by macrophages and that macrophage-synthesized melatonin modulates the function of these professional phagocytes in an autocrine manner. Expression of a DsRed2 fluorescent reporter driven by regions of the aa-nat promoter, that en...

The pineal gland, a circumventricular organ, plays an integrative role in defense responses. The injury-induced suppression of the pineal gland hormone, melatonin, which is triggered by darkness, allows the mounting of innate immune responses. We have previously shown that cultured pineal glands, which express toll-like receptor 4 (TLR4) and tumor...

  The endothelial layer regulates the traffic of cells and substances between the blood and tissues and plays a central role in the mounting of an inflammatory response. We have recently shown that inhibition of the nocturnal melatonin surge during the mounting of an inflammatory response primes endothelial cells to a highly reactive state, increas...

Shiftwork-induced sleep deprivation and circadian disruption probably leads to an increase in the production of cytokines and dysregulation of innate immune system, respectively. This project aims evaluating changes in salivary IL-1 beta, cortisol, and melatonin in night workers. Method. Two day and three night healthy workers participated in this...

The 18 kDa translocator protein (TSPO) also known as the peripheral benzodiazepine receptor (PBR), mediates the transportation of cholesterol and anions from the outer to the inner mitochondrial membrane in different cells types. Although recent evidences indicate a potential role for TSPO in the development of inflammatory processes, the mechanism...

We evaluated how the mild stress-induced increase in endogenous corticosterone affected the pineal gland in Syrian hamsters (Mesocricetus auratus). The animals were maintained under constant light for 1 day, instead of a cycle of 14:10-h, to increase the circulating corticosterone levels during the daytime. The nuclear translocation of nuclear fact...

This study established the value of the 6‐sulfatoxymelatonin (aMT6s) urine concentration as a predictor of the therapeutic response to noradrenaline reuptake inhibitors in depressive patients. Twenty-two women aged 18-60 years were selected. Depressive symptoms were assessed by using the Hamilton Depression Scale. Urine samples were collected at 06...

The pineal gland, the gland that translates darkness into an endocrine signal by releasing melatonin at night, is now considered a key player in the mounting of an innate immune response. Tumor necrosis factor (TNF), the first pro-inflammatory cytokine to be released by an inflammatory response, suppresses the translation of the key enzyme of melat...

We have shown previously that nitric oxide (NO) controls platelet endothelial cell adhesion molecule (PECAM-1) expression on both neutrophils and endothelial cells under physiological conditions. Here, the molecular mechanism by which NO regulates lipopolysaccharide (LPS)-induced endothelial PECAM-1 expression and the role of interleukin (IL)-10 on...

Melatonin is an indolamine with a large spectrum of functions that can be divided into chronobiotic and nonchronobiotic. Chronobiotic effects are mediated by the daily rhythm of melatonin in the plasma due to nocturnal pineal synthesis, whereas the melatonin produced by other cells, such as gastrointestinal and immune competent cells, is independen...

Participation of the pineal gland and melatonin in the innate immune response is part of a dynamic and intricate network that acts throughout the inflammatory response, integrating signaling pathways and regulatory processes at the molecular, cellular and organism levels. The pineal gland is a target for pathogen-associated molecular patterns and f...

Receptores nicotínicos da acetilcolina são encontrados na retina de pintos desde o início do desenvolvimento embrionário. As propostas desse trabalho foram caracterizar esses receptores no desenvolvimento de células de retinas embrionárias de pinto com oito dias, em cultura, e investigar se luzindole, um antagonista de receptores de melatonina, int...