The sympathetic nervous system and the immune system are responsible for producing neurotransmitters and cytokines that interact by binding to receptors; due to this, there is communication between ...these systems. Liver immune cells and nerve fibres are systematically distributed in the liver, and the partial overlap of both patterns may favour interactions between certain elements. Dendritic cells are attached to fibroblasts, and nerve fibres are connected via the dendritic cell-fibroblast complex. Receptors for most neuroactive substances, such as catecholamines, have been discovered on dendritic cells. The sympathetic nervous system regulates hepatic fibrosis through sympathetic fibres and adrenaline from the adrenal glands through the blood. When there is liver damage, the sympathetic nervous system is activated locally and systemically through proinflammatory cytokines that induce the production of epinephrine and norepinephrine. These neurotransmitters bind to cells through α-adrenergic receptors, triggering a cellular response that secretes inflammatory factors that stimulate and activate hepatic stellate cells. Hepatic stellate cells are key in the fibrotic process. They initiate the overproduction of extracellular matrix components in an active state that progresses from fibrosis to liver cirrhosis. It has also been shown that they can be directly activated by norepinephrine. Alpha and beta adrenoblockers, such as carvedilol, prazosin, and doxazosin, have recently been used to reverse CCl
4
-induced liver cirrhosis in rodent and murine models.
KEY MESSAGES
Neurotransmitters from the sympathetic nervous system activate and increase the proliferation of hepatic stellate cells.
Hepatic fibrosis and cirrhosis treatment might depend on neurotransmitter and hepatic nervous system regulation.
Strategies to reduce hepatic stellate cell activation and fibrosis are based on experimentation with α-adrenoblockers.
The aim of this study was to evaluate the inflammation process that resulted from the inoculation of Wistar Rats with Acanthamoeba griffini, a virulent T3 Acanthamoeba genotype that produces ...keratitis. Haematoxylin and eosin, periodic acid stain, immunohistochemistry and morphometry were used to analyse tissues from rats of an Acanthamoeba keratitis (AK) model. Two weeks after inoculating the rats with A griffini trophozoites, the thickness of the stroma had diminished, followed by an increase in thickness at 4 weeks. At the latter time, an abundance of inflammatory infiltrate cells was observed, some found to express IL‐1β, IL‐10 and/or caspase 3. Intercellular adhesion molecule‐1 was expressed in corneal blood vessels amid the abundant vascularization characteristic of the development of AK. Through an immunohistochemical technique, trophozoites were detected at 2 and 4 weeks post‐inoculation. By 8 weeks, there were a low number of trophozoites and cysts and the corneas of infected rats were similar in thickness to those of the controls. Thus, the rats were capable of healing experimental AK in the present rat model. Diverse immunological mechanisms regulated the inflammatory process in acute AK induced by A griffini in a murine model.
is an anaerobic parasitic protozoan and the causative agent of amoebiasis.
expresses proteins that are structurally homologous to human proteins and uses them as virulence factors. We have previously ...shown that
binds exogenous interferon gamma (IFN-γ) on its surface, and in this study, we explored whether exogenous IFN-γ could modulate parasite virulence. We identified an IFN-γ receptor-like protein on the surface of
trophozoites by using anti-IFN-γ receptor 1 (IFN-γR1) antibody and performing immunofluorescence, Western blot, protein sequencing, and
analyses. Coupling of human IFN-γ to the IFN-γ receptor-like protein on live
trophozoites significantly upregulated the expression of
cysteine protease A1 (
CP-A1),
CP-A2,
CP-A4,
CP-A5, amebapore A (APA), cyclooxygenase 1 (
), Gal-lectin (
), and peroxiredoxin (
) in a time-dependent fashion. IFN-γ signaling via the IFN-γ receptor-like protein enhanced
's erythrophagocytosis of human red blood cells, which was abrogated by the STAT1 inhibitor fludarabine. Exogenous IFN-γ enhanced chemotaxis of
, its killing of Caco-2 colonic and Hep G2 liver cells, and amebic liver abscess formation in hamsters. These results demonstrate that
expresses a surface IFN-γ receptor-like protein that is functional and may play a role in disease pathogenesis and/or immune evasion.
The parasite Entamoeba histolytica is the causal agent of amoebiasis, a worldwide emerging disease. Amebic brain abscess is a form of invasive amebiasis that is both rare and frequently lethal. This ...condition always begins with the infection of the colon by E. histolytica trophozoites, which subsequently travel through the bloodstream to extraintestinal tissues.
We report a case of a 71-year-old female who reported an altered state of consciousness, disorientation, sleepiness and memory loss. She had no history of hepatic or intestinal amoebiasis. A preliminary diagnosis of colloidal vesicular phase neurocysticercosis was made based on nuclear magnetic resonance imaging (NMRI). A postsurgery immunofluorescence study was positive for the 140 kDa fibronectin receptor of E. histolytica, although a serum analysis by ELISA was negative for IgG antibodies against this parasite. A specific E. histolytica 128 bp rRNA gene was identified by PCR in biopsy tissue. The final diagnosis was cerebral amoebiasis. The patient underwent neurosurgery to eliminate amoebic abscesses and was then given a regimen of metronidazole, ceftriaxone and dexamethasone for 4 weeks after the neurosurgery. However, a rapid decline in her condition led to death.
The present case of an individual with a rare form of cerebral amoebiasis highlights the importance of performing immunofluorescence, NMRI and PCR if a patient has brain abscess and a poorly defined diagnosis. Moreover, the administration of corticosteroids to such patients can often lead to a rapid decline in their condition.
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•Watercress extract could prevent the progression of liver fibrosis.•Watercress extract restores the levels of NRF2 in the liver and the overexpression of IL-10 in both the liver and ...intestine.•Watercress extract reduced the hepatic expression of the fibrogenic factor TGF-β and the pro-inflammatory cytokine IL-1.•Watercress extract has the potential to serve as a natural therapeutic alternative for liver fibrosis.
The present study aimed to analyze the antioxidant and hepatoprotective efficacy of watercress extract against liver fibrosis induced by CCl4 (0.8 mL/kg, i.p) in an in vivo rat model. Four groups were included, each with five animals (n = 5): 1) Intact, 2) CCl4-induced for 4 weeks, 3) CCl4-induced for 8 weeks, and 4) CCl4-induced for 4 weeks followed by watercress extract treatment (600 mg/kg/day) until week 8. Tissue samples were analyzed using histological techniques (H&E, Sirius Red, Masson's trichrome stain), biochemical methods, and gene expression analysis of IL-1, IL-10, TGF-β, NRF2, Keap1, Acta2, Timp-2, MMP-13, and MMP-9. Watercress extract administration resulted in improvements by preventing steatosis and fibrosis. It also increased IL-10 expression in the liver and intestine. Additionally, the expression of fibrogenic markers such as TGF-β, Col 1α, Acta2, and Timp-2 was regulated. These results suggest that orally administered watercress extract prevents the progression of liver fibrosis.
A molecular characterization of the main phytochemicals and antioxidant activity of
(OR) fruit extract was carried out, as well as an evaluation of its hepatoprotective effect against diclofenac ...(DF)-induced acute liver injury was evaluated. Phenols, flavonoids and betalains were quantified, and antioxidant characterization was performed by means of the ABTS
, DPPH and FRAP assays. UPLC-QTOF-MS/MS was used to identify the main biocompounds present in OR fruit extract was carried out via. In the in vivo model, groups of rats were treated prophylactically with the OR fruit extract, betanin and
-acteylcysteine followed by a single dose of DF. Biochemical markers of oxidative stress (MDA and GSH) and relative gene expression of the inducible antioxidant response (
,
,
,
and
), cell death (
) and DNA repair (
) were analyzed. Western blot analysis was performed to measure protein levels of Nrf2 and immunohistochemical analysis was used to assess caspase-3 activity in the experimental groups. In our study, the OR fruit extract showed strong antioxidant and cytoprotective capacity due to the presence of bioactive compounds, such as betalain and phenols. We conclude that OR fruit extract or selected components can be used clinically to support patients with acute liver injury.
Entamoeba histolytica is an intestinal parasite that causes dysentery and amebic liver abscess. E. histolytica has the capability to invade host tissue by union of virulence factor Gal/GalNAc lectin; ...this molecule induces an adherence-inhibitory antibody response as well as to protect against amebic liver abscess (ALA). The present work showed the effect of the immunization with PEΔIII-LC3-KDEL3 recombinant protein. In vitro, this candidate vaccine inhibited adherence of E. histolytica trophozoites to HepG2 cell monolayer, avoiding the cytolysis, and in a hamster model, we observed a vaccine-induced protection against the damage to tissue liver and the inhibition of uncontrolled inflammation. PEΔIII-LC3-KDEL3 reduced the expression of TNF-α, IL-1β, and NF-κB in all immunized groups at 4- and 7-day postinfection. The levels of IL-10, FOXP3, and IFN-γ were elevated at 7 days. The immunohistochemistry assay confirmed this result, revealing an elevated quantity of +IFN-γ cells in the liver tissue. ALA formation in hamsters immunized was minimal, and few trophozoites were identified. Hence, immunization with PEΔIII-LC3-KDEL3 herein prevented invasive amebiasis, avoided an acute proinflammatory response, and activated a protective response within a short time. Finally, this recombinant protein induced an increase of serum IgG.
is an invasive enteric protozoan, whose infections are associated to high morbidity and mortality rates. However, only less than 10% of infected patients develop invasive amebiasis. The ability of
to ...adapt to the intestinal microenvironment could be determinant in triggering pathogenic behavior. Indeed, during chronic inflammation, the vagus nerve limits the immune response through the anti-inflammatory reflex, which includes acetylcholine (ACh) as one of the predominant neurotransmitters at the infection site. Consequently, the response of
trophozoites to ACh could be implicated in the establishment of invasive disease. The aim of this study was to evaluate the effect of ACh on
virulence. Methods include binding detection of ACh to plasma membrane, quantification of the relative expression of virulence factors by RT-PCR and western blot, evaluation of the effect of ACh in different cellular processes related to
pathogenesis, and assessment of the capability of
to migrate and form hepatic abscesses in hamsters. Results demonstrated that
trophozoites bind ACh on their membrane and show a clear increase of the expression of virulence factors, that were upregulated upon stimulation with the neurotransmitter. ACh treatment increased the expression of L220,
heavy subunit (170 kDa),
, cysteine proteinase 2 (
), and cysteine proteinase 5 (
). Moreover, erythrophagocytosis, cytotoxicity, and actin cytoskeleton remodeling were augmented after ACh treatment. Likewise, by assessing the formation of amebic liver abscess, we found that stimulated trophozoites to develop greater hamster hepatic lesions with multiple granulomas. In conclusion, ACh enhanced parasite pathogenicity by upregulating diverse virulence factors, thereby contributing to disease severity, and could be linked to the establishment of invasive amebiasis.
Host invasion by Entamoeba histolytica, the pathogenic agent of amebiasis, can lead to the development of amebic liver abscess (ALA). Due to the difficulty of exploring host and amebic factors ...involved in the pathogenesis of ALA in humans, most studies have been conducted with animal models (e.g., mice, gerbils, and hamsters). Histopathological findings reveal that the chronic phase of ALA in humans corresponds to lytic or liquefactive necrosis, whereas in rodent models there is granulomatous inflammation. However, the use of animal models has provided important information on molecules and mechanisms of the host/parasite interaction. Hence, the present review discusses the possible role of neutrophils in the effector immune response in ALA in rodents. Properly activated neutrophils are probably successful in eliminating amebas through oxidative and non-oxidative mechanisms, including neutrophil degranulation, the generation of free radicals (O2−, H2O2, HOCl) and peroxynitrite, the activation of NADPH-oxidase and myeloperoxidase (MPO) enzymes, and the formation of neutrophil extracellular traps (NETs). On the other hand, if amebas are not eliminated in the early stages of infection, they trigger a prolonged and exaggerated inflammatory response that apparently causes ALAs. Genetic differences in animals and humans are likely to be key to a successful host immune response.
L’invasion d’un hôte par Entamoeba histolytica, l’agent pathogène de l’amibiase, peut conduire au développement d’un abcès hépatique amibien (AHA). En raison de la difficulté d’explorer les facteurs dépendant de l’hôte et des amibes impliqués dans la pathogenèse de l’AHA chez les humains, la plupart des études ont été menées sur des modèles animaux (par exemple souris, gerbilles et hamsters). Les résultats histopathologiques montrent que la phase chronique de l’AHA chez l’homme correspond à la nécrose lytique ou liquéfiante, tandis que dans les modèles rongeurs on rencontre une inflammation granulomateuse. Cependant, l’utilisation de modèles animaux a fourni des informations importantes sur les molécules et les mécanismes de l’interaction hôte/parasite. Cette synthèse discute donc le rôle possible des neutrophiles dans la réponse immunitaire effectrice pendant l’AHA chez les rongeurs. Les neutrophiles correctement activés réussissent probablement à éliminer les amibes grâce à des mécanismes oxydatifs et non oxydatifs, y compris la dégranulation des neutrophiles, la génération de radicaux libres (O2−, H2O2, HOCl) et de peroxynitrite, l’activation des enzymes NADPH-oxydase et myéloperoxydase, et la formation de pièges extracellulaires des neutrophiles. D’autre part, si les amibes ne sont pas éliminées au cours des premiers stades de l’infection, elles déclenchent une réponse inflammatoire prolongée et excessive qui provoque apparemment l’AHA. Les différences génétiques chez les animaux et les humains sont probablement la clé d’une réponse immunitaire réussie de l’hôte.
Bioaccumulation of trivalent (CrIII) and hexavalent chromium (CrVI), and its adverse effects were studied in two rotifer species: Brachionus calyciflorus (two different strains), and Lecane ...quadridentata. Median Lethal Concentration (LC50) at 24 h of both species showed that CrVI is highly toxic: LC50 ranges from 4.7 × 10−5 to 4 × 10−6 mg L−1), compared with CrIII: LC50 ranges from 0.64 to 1.279 mg L−1. Using the LC50 as an exposure concentration, and using atomic absorption, the bioconcentration factor (BCF) was obtained and BCFs of rotifers exposed to CrIII are four orders of magnitude lower than BCFs of rotifers exposed to CrVI. The effect of Cr on the elemental composition of the two species of rotifers in their structures by X-ray microanalysis by energy dispersion showed that Cr is found in intoxicated rotifers, but not in control rotifers. The basal immunoreactivity to metallothioneins is greater in B. calyciflorus than L. quadridentata. The immunoreactivity to metallothioneins decreases in B. calyciflorus when is exposed to CrIII, in contrast in L. quadridentata the immunoreactivity to metallothioneins increase when is exposed to CrIII, and the immunoreactivity to CrVI in L. quadridentata decrease. A mechanism is proposed in which the harder lorica of L. quadridentata acts as a barrier and accumulator of CrVI, and allows for attenuating responses like metallothionein production in L. quadridentata. Instead, in B. calyciflorus the lack of a harder lorica allows for deeper penetration of CrVI, and no time to produce attenuating measures.
•Bioaccumulation of Cr III and Cr VI and its adverse effects were studied in two rotifer species.•For Cr VI, 24-h LC50 ranged from 4.7 × 10−5 to 4 × 10−6 mg/L, whereas that for Cr III ranged from 0.64 to 1.279 mg/L.•Bioconcentration factors (BCFs) of Cr III rotifers are four orders of magnitude higher than those of Cr VI.•X-ray microanalysis showed that Cr is found in intoxicated rotifers, but not in control ones.•Harder lorica of Lecane quadridentata acts as a barrier and accumulator of Cr VI.
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