Chagasic antibodies induce cardiac COX-2/iNOS mRNA expression with PGE2/NO production

Ganzinelli, Sabrina; Borda, Enri; Joensen, Lilian; Sterin‐Borda, Leonor

doi:10.1016/j.ijcard.2008.02.008

Cited by 14 publications

(16 citation statements)

References 34 publications

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“…Ashton et al (Ashton et al, 2007) demonstrated that TXA2 is an important factor in Chagas disease that controls parasite proliferation and the resulting inflammatory response to the infection. TXA2 is a potent proinflammatory agent that activates and facilitates cytokine production by monocytes (Caughey et al, 1997;Ganzinelli et al, 2009). TXA2 activates endothelial cells, mediating inflammatory responses, through i) increased vascular permeability; ii) increased adhesion molecule expression; and iii) leukocyte adhesion to the vessel wall (Patrono et al, 2005).…”

Section: Microvascular Abnormalities and Ischemiamentioning

confidence: 99%

“…Thus, PGE2 contributes towards cardiac remodeling and functional deficits after infection by T. cruzi (Freire-de-Lima et al, 2000). Prostaglandin synthesis during T. cruzi infection is related to nitric oxide production (Durand et al, 2009;Ganzinelli et al, 2009). At least two mechanisms of oxidative stress exists, dependent or independent, with regard to the nitric oxide and cyclooxygenase pathway, where one or the other is more evident depending on the cell type or mouse strain (Freirede-Lima et al, 2006;Ganzinelli et al, 2009;Hideko Tatakihara et al, 2008;Silva et al, 2003).…”

Section: Role Of Prostaglandins In the Pathogenesis Of Chagas Diseasementioning

confidence: 99%

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Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

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Section: Microvascular Abnormalities and Ischemiamentioning

confidence: 99%

Section: Role Of Prostaglandins In the Pathogenesis Of Chagas Diseasementioning

confidence: 99%

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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“…The dysautonomia described in Chagasic cardiomyopathy and GI dysmotility is strongly associated with the presence of autoantibodies as detected by the anti-M 2 peptide ELISA with 90% of patients with a measurable autonomic disturbance testing positive, compared with less than 30% with no disturbance and in no healthy controls Ganzinelli et al 2009). These autoantibodies have been detected in 84% of patients with chagasic achalasia versus 21% of those with Chagas' disease but no oesophageal sequalae and 28% in idiopathic achalasia (Goin et al 1999).…”

Section: Specificity For Diseasementioning

confidence: 99%

“…An increase in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene transcription is observed in response to chagasic IgG application, increasing prostaglandin E2 (PGE 2 ) and nitric oxide (NO) production (Ganzinelli et al 2009). This has pathological relevance to the end-organ inflammation seen in chronic Chagas disease.…”

Section: Modulation Of Antigen Expression and / Or Functional Effectsmentioning

confidence: 99%

“…To help answer the question of whether the present cohort have autoantibodies which activate muscarinic pathways without binding receptors directly or have another mechanism of action, we proceeded to investigate the functional effects of the sera from our cohort on GI smooth muscle. cholinergic signalling pathway with subsequent end organ effects Goin et al 1997;Sterin-Borda et al 1997;Hernandez et al 2008;Ganzinelli et al 2009) including an increase in GI smooth muscle tone (Goin et al 1999;SterinBorda et al 2001). It should be noted that the majority of these studies originate from a single research group, and all studies have used the same ELISA to detect anti-M 2 mAChR autoantibodies.…”

Section: Significance and Interpretationsmentioning

confidence: 99%

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The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Hubball

Martin

Lang

et al. 2009

Progress in Neurobiology

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Dysfunction of the gastrointestinal neuromuscular apparatus (including interstitial cells ofCajal) is presumed to underlie a heterogeneous group of disorders collectively termed gastrointestinal neuromuscular diseases (GINMDs). Humoral (antibody)-mediated autoimmunity directed against ligand-or voltage-gated ion channels or associated proteins involved in neuromuscular transmission is associated with several acquired neuromuscular diseases of the periphery and is now implicated in an increasing number of less well-characterised diseases. Anti-channel antibodies have been reported in small numbers of patients with GINMD, particularly in those with GI dysfunction secondary to an underlying disease such as neoplasia or infection. However, little is known of humoral autoimmunity in primary GINMDs.This thesis investigated the association between anti-channel antibodies and GINMD, and the human GI tract as a potential target of anti-channel antibodies. The presence of antivoltage-and ligand-gated antibodies was investigated in the serum of patients with primary achalasia, enteric dysmotility and intestinal pseudo-obstruction, and in those with GINMD secondary to Chagas' disease. The functional effect of sera from some of these patients on colonic smooth muscle contractility was also characterised. Finally, the distribution of six voltage-gated potassium channels (VGKCs), which serve essential roles in the peripheral and central nervous systems and are known targets of pathological autoantibodies, were investigated in all layers of the human GI tract.Our findings suggest that currently recognised anti-channel antibodies are not a common pathogenic factor in primary GINMDs. Anti-channel antibodies, in particular anti-VGKC antibodies, were however found in a significant number of individuals with Chagas' disease. Furthermore, circulating factors in patients with chagasic GI disease altered GI smooth muscle contractility in vitro which may have pathological relevance to GI

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Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways

Song

Jiang

et al. 2021

Immunity Inflam & Disease

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Introduction Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO‐1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO‐1 pathways in asthma is unclear. Herein, we aim to explore the pharmacological effects of Pts on oxidative stress and allergic inflammatory response as well as the mechanism involving AMPK/Sirt1 and Nrf2/HO‐1 pathways. Methods Asthma model was established in mice with ovalbumin (OVA). The model mice were treated by different concentrations of Pts. Lung pathological changes were observed through histological staining. In vitro, lipopolysaccharide (LPS)‐stimulated 16HBE cells were treated with Pts. The siAMPKα2, siSirt1 and siNrf2 knockdown, and treatment with compound C, EX‐527 or ML385 were also performed in 16HBE cells. Enzyme‐linked immunosorbent assay was used to detect interleukin‐4 (IL‐4), IL‐13, IL‐5, total and OVA specific immunoglobulin E (IgE), and interferon γ (IFN‐γ). Pneumonography was used to measure the airway hyperreactivity (AHR). Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were also detected. Immunohistochemistry, Western blot and immunofluorescence were used to measure protein levels. Results Pts significantly attenuated lung inflammatory cell infiltration and goblet cell proliferation. Meanwhile, Pts treatment could reduce IL‐4, IL‐13, IL‐5, and IgE (total and OVA specific) levels in the asthma model mice. However, IFN‐γ in bronchoalveolar lavage fluid was elevated. In addition, Pts reduced AHR. We also found that Pts treatment promoted serum SOD and CAT, and reduced MDA. In vitro results showed that Pts treatment promoted iNOS, TNF‐α, COX‐2, IL‐1β, and IL‐6 expressions in 16HBE cells, prolonged G0/G1 phase of the cell cycle, and resulted in a shortened G2M phase. Moreover, we found that Pts promoted the phosphorylation of AMPK in 16HBE, and meanwhile inhibited the increase of ROS induced by LPS. Additionally, Pts treatment inhibited p‐AMPK, Sirt1, Nrf2 and HO‐1, which in turn leads to the alleviation of AMPK/Sirt1 and Nrf2/HO‐1 pathways. Conclusion Pts alleviated oxidative stress and allergic airway inflammation via regulation of AMPK/Sirt1and Nrf2/HO‐1 signaling pathways.

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Chagasic antibodies induce cardiac COX-2/iNOS mRNA expression with PGE2/NO production

Cited by 14 publications

References 34 publications

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways

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