Endogenous PGD2 acting on DP2 receptor counter regulates Schistosoma mansoni infection-driven hepatic granulomatous fibrosis.

Identifying new molecular therapies targeted at the severe hepatic fibrosis associated with the granulomatous immune response to Schistosoma mansoni infection is essential to reduce fibrosis-related morbidity/mortality in schistosomiasis. In vitro cell activation studies suggested the lipid molecule prostaglandin D2 (PGD2) as a potential pro-fibrotic candidate in schistosomal context, although corroboratory in vivo evidence is still lacking. Here, to investigate the role of PGD2 and its cognate receptor DP2 in vivo, impairment of PGD2 synthesis by HQL-79 (an inhibitor of the H-PGD synthase) or DP2 receptor inhibition by CAY10471 (a selective DP2 antagonist) were used against the fibrotic response of hepatic eosinophilic granulomas of S.

Parasitic infections: A new frontier for PGD functions.

Prostaglandin (PG)D is produced and/or triggered by different parasites to modulate the course of the infection. These findings position PGD2 as a therapeutic target and suggest potential beneficial effects of repositioned drugs that target its synthesis or receptor engagement. However, recent data may suggest a more nuanced role and warrants further investigation of the role of PGD2 during the full course and complexity of parasitic infections.

COVID-19 diverse outcomes: Aggravated reinfection, type I interferons and antibodies.

SARS-CoV-2 infection intrigued medicine with diverse outcomes ranging from asymptomatic to severe acute respiratory syndrome (SARS) and death. After more than two years of pandemic, reports of reinfection concern researchers and physicists. Here, we will discuss potential mechanisms that can explain reinfections, including the aggravated ones.

Acute catabolism of leukocyte lipid bodies: Characterization of a nordihydroguaiaretic acid (NDGA)-induced proteasomal-dependent model.

Cytoplasmic availability of leukocyte lipid bodies is controlled by a highly regulated cycle of opposing biogenesis- and catabolism-related events. While leukocyte biogenic machinery is well-characterized, lipid body catabolic mechanisms are yet mostly unknown. Here, we demonstrated that nordihydroguaiaretic acid (NDGA) very rapidly decreases the numbers of pre-formed lipid bodies within lipid body-enriched cytoplasm of mouse leukocytes - macrophages, neutrophils and eosinophils.

Eosinophils increase macrophage ability to control intracellular Leishmania amazonensis infection via PGD paracrine activity in vitro.

Clinical and experimental studies have described eosinophil infiltration in Leishmania amazonensis infection sites, positioning eosinophils strategically adjacent to the protozoan-infected macrophages in cutaneous leishmaniasis. Here, by co-culturing mouse eosinophils with L. amazonensis-infected macrophages, we studied the impact of eosinophils on macrophage ability to regulate intracellular L.

Prostaglandins regulate humoral immune responses in Aedes aegypti.

Prostaglandins (PGs) are immuno-active lipids that mediate the immune response in invertebrates and vertebrates. In insects, PGs play a role on different physiological processes such as reproduction, ion transport and regulation of cellular immunity. However, it is unclear whether PGs play a role in invertebrate's humoral immunity, and, if so, which immune signaling pathways would be modulated by PGs.

Inflammatory profiling of patients with familial amyloid polyneuropathy.

Background: Familial amyloid polyneuropathy (FAP) or ATTRv (amyloid TTR variant) amyloidosis is a fatal hereditary disease characterized by the deposition of amyloid fibrils composed of transthyretin (TTR). The current diagnosis of ATTRv relies on genetic identification of TTR mutations and on Congo Red-positive amyloid deposits, which are absent in most ATTRv patients that are asymptomatic or early symptomatic, supporting the need for novel biomarkers to identify patients in earlier disease phases allowing disease control.

Methods: In an effort to search for new markers for ATTRv, our group searched for nine inflammation markers in ATTRv serum from a cohort of 28 Brazilian ATTRv patients.

Schistosomal Lipids Activate Human Eosinophils via Toll-Like Receptor 2 and PGD Receptors: 15-LO Role in Cytokine Secretion.

Parasite-derived lipids may play important roles in host-pathogen interactions and immune evasion mechanisms. Remarkable accumulation of eosinophils is a characteristic feature of inflammation associated with parasitic disease, especially caused by helminthes. Infiltrating eosinophils are implicated in the pathogenesis of helminth infection by virtue of their capacity to release an array of tissue-damaging and immunoregulatory mediators.

Leptin Elicits LTC Synthesis by Eosinophils Mediated by Sequential Two-Step Autocrine Activation of CCR3 and PGD Receptors.

Leptin is a cytokine, produced mainly by mature adipocytes, that regulates the central nervous system, mainly to suppress appetite and stimulate energy expenditure. Leptin also regulates the immune response by controlling activation of immunomodulatory cells, including eosinophils. While emerging as immune regulatory cells with roles in adipose tissue homeostasis, eosinophils have a well-established ability to synthesize pro-inflammatory molecules such as lipid mediators, a key event in several inflammatory pathologies.

Leptin Mediates Neutrophil Migration: Involvement of Tumor Necrosis Factor-Alpha and CXCL1.

Leptin directly activates macrophages and lymphocytes, but the role of leptin in neutrophil activation and migration is still controversial. Here, we investigate the mechanisms of neutrophil migration induced by leptin. The intraperitoneal injection of leptin (1 mg/kg) induces a time- and concentration-dependent neutrophil influx.

Corrigendum: Differential Regulation of Thyroid Hormone Metabolism Target Genes during Non-thyroidal Illness Syndrome Triggered by Fasting or Sepsis in Adult Mice.

[This corrects the article on p. 828 in vol. 8, PMID: 29118715.

Differential Regulation of Thyroid Hormone Metabolism Target Genes during Non-thyroidal [corrected] Illness Syndrome Triggered by Fasting or Sepsis in Adult Mice.

Fasting and sepsis induce profound changes in thyroid hormone (TH) central and peripheral metabolism. These changes affect TH action and are called the non-thyroidal illness syndrome (NTIS). To date, it is still debated whether NTIS represents an adaptive response or a real hypothyroid state at the tissue level.

Resolvin D1 drives establishment of Leishmania amazonensis infection.

Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators.

EicosaCell: An Imaging-Based Assay to Identify Spatiotemporal Eicosanoid Synthesis.

Eicosanoids are bioactive lipids derived from enzymatic metabolism of arachidonic acid via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. These lipids are newly formed and nonstorable molecules that have important roles in physiological and pathological processes. The particular interest to determine intracellular compartmentalization of eicosanoid-synthetic machinery has emerged as a key component in the regulation of eicosanoid synthesis and in delineating functional intracellular and extracellular actions of eicosanoids.

Hepatic myofibroblasts derived from Schistosoma mansoni-infected mice are a source of IL-5 and eotaxin: controls of eosinophil populations in vitro.

Background: Hepatic myofibroblasts are relevant for pathogenesis of S. mansoni infection. In normal liver, these perisinusoidal cells are quiescent, express the lipocyte phenotype, and are located in the Disse's space, being the major site of vitamin A storage.

Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.

Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S.

The PGE2/IL-10 Axis Determines Susceptibility of B-1 Cell-Derived Phagocytes (B-1CDP) to Leishmania major Infection.

B-1 cells can be differentiated from B-2 cells because they are predominantly located in the peritoneal and pleural cavities and have distinct phenotypic patterns and activation properties. A mononuclear phagocyte derived from B-1 cells (B-1CDP) has been described. As the B-1CDP cells migrate to inflammatory/infectious sites and exhibit phagocytic capacity, the microbicidal ability of these cells was investigated using the Leishmania major infection model in vitro.

Schistosome infection-derived Hepatic Stellate Cells are cellular source of prostaglandin D₂: role in TGF-β-stimulated VEGF production.

Hepatic Stellate Cells (HSCs) play a crucial role in pathogenesis of liver inflammation and fibrosis. During chronic liver injury, HSCs lose vitamin A and transform into myofibroblastic cells. In schistosomal granulomas, these activated HSCs are called GR-HSCs.

Understanding the mechanisms controlling Leishmania amazonensis infection in vitro: the role of LTB4 derived from human neutrophils.

Neutrophils are rapidly recruited to the site of Leishmania infection and play an active role in capturing and killing parasites. They are the main source of leukotriene B4 (LTB4), a potent proinflammatory lipid mediator. However, the role of LTB4 in neutrophil infection by Leishmania amazonensis is not clear.

Eosinophil recruitment and activation: the role of lipid mediators.

Eosinophils are effector cells that migrate toward several mediators released at inflammatory sites to perform their multiple functions. The mechanisms driving eosinophil selective accumulation in sites of allergic inflammation are well-established and involve several steps controlled by adhesion molecules, priming agents, chemotactic, and surviving factors. Even though the majority of studies focused on role of protein mediators like IL-5 and eotaxins, lipid mediators also participate in eosinophil recruitment and activation.

Effectiveness of Cissampelos sympodialis and its isolated alkaloid warifteine in airway hyperreactivity and lung remodeling in a mouse model of asthma.

Background: Cissampelos sympodialis Eichl. (Menispermaceae) is a plant found in Northeastern and Southeast of Brazil and hot water infusion of C. sympodialis root bark is largely used in the indigenous and folk medicine to treat several inflammatory disorders, including asthma.

Eosinophils as a novel cell source of prostaglandin D2: autocrine role in allergic inflammation.

PGD(2) is a key mediator of allergic inflammatory diseases that is mainly synthesized by mast cells, which constitutively express high levels of the terminal enzyme involved in PGD(2) synthesis, the hematopoietic PGD synthase (H-PGDS). In this study, we investigated whether eosinophils are also able to synthesize, and therefore, supply biologically active PGD(2). PGD(2) synthesis was evaluated within human blood eosinophils, in vitro differentiated mouse eosinophils, and eosinophils infiltrating inflammatory site of mouse allergic reaction.

Lipid body function in eicosanoid synthesis: an update.

Eicosanoids (prostaglandins, leukotrienes and lipoxins) are signaling lipids derived from arachidonic acid metabolism that have important roles in physiological and pathological processes. Lately, intracellular compartmentalization of eicosanoid-synthetic machinery has emerged as a key component in the regulation of eicosanoid synthesis and functions. Over the past years substantial progresses have been made demonstrating that precursors and enzymes involved in eicosanoid synthesis localize at lipid bodies (also known as lipid droplets) and lipid bodies are distinct sites for eicosanoid generation.