IL-10 Inhibits the NF-κB and ERK/MAPK-Mediated Production of Pro-Inflammatory Mediators by Up-Regulation of SOCS-3 in Trypanosoma cruzi-Infected Cardiomyocytes

Hovsepian, Eugenia; Penas, Federico Nicolás; Siffo, Sofía; Mirkin, Gerardo A.; Goren, Nora

doi:10.1371/journal.pone.0079445

Cited by 65 publications

(63 citation statements)

References 48 publications

(64 reference statements)

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“…Our results demonstrated that upon Ang II stimulation, exogenous IL‐10 plays an inhibitory role in vascular ERK 1/2 activation. Similarly, exogenous IL‐10 inhibits ERK 1/2 activation and other proteins related to cellular remodeling in cardiomyocytes infected with Trypanosoma cruzi . IL‐10 inhibits the activation of macrophages and granulocytes by decreasing the production of reactive oxygen species, via inactivation of ERK 1/2 and modulation of NADPH oxidase .…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐10 negatively modulates extracellular signal‐regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion

Bressan

Fonseca

Tostes

et al. 2018

Fundamemntal Clinical Pharma

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The activation of extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathway promotes increased vascular contractility in angiotensin II (Ang II)-induced hypertensive mice. Interleukin-10 (IL-10) is an immune-regulatory cytokine with the ability to prevent vascular hypercontractility during hypertension. We hypothesized that IL-10 would downregulate vascular ERK 1/2 activation during Ang II-induced hypertension. Wild-type (WT) or IL-10 knockout (IL-10 ) mice received Ang II infusion (90 ηg.min) or vehicle (saline), via osmotic mini-pumps (0.25 μL/h for 14 days), whereas another WT group were infused with exogenous IL-10 (0.5 ηg/min, 14 days) simultaneously, or not, with Ang II. Aortic rings were mounted in a myograph, and concentration-response curves to phenylephrine were evaluated, in the presence or absence of ERK 1/2 inhibitor (PD98059, 10 μm, 40 min). Protein expression of vascular ERK 1/2 was determined by Western blot. Ang II infusion increased the maximal contractile response in both WT and IL-10 mice. Concomitant infusion of IL-10 and Ang II prevented hypercontractility in the vasculature. Exogenous IL-10 infusion prevented ERK 1/2 activation and hypercontractility, induced by Ang II. These findings suggest that IL-10 negatively modulates ERK 1/2 activation and prevents hypercontractility during Ang II-induced hypertension.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐10 negatively modulates extracellular signal‐regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion

Bressan

Fonseca

Tostes

et al. 2018

Fundamemntal Clinical Pharma

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“…The degradation of IjB is necessary for the translocation of NF-jB to the nucleus and subsequent binding to DNA. IKK plays a role in the phosphorylation and degradation of IjB (Clarke et al 1998;Hovsepian et al 2013). We next examined IjB and the phosphorylation of IKKa/b in these cells by Western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

Viral IL-10 down-regulates the “MHC-I antigen processing operon” through the NF-κB signaling pathway in nasopharyngeal carcinoma cells

et al. 2016

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“…This finding, together with the observations that both exogenous NO administration [46] and endogenous NO production [41] prevent cardiac hypertrophy and that eNOS −/− mice develop pressure overload‐induced / age‐related myocardial hypertrophy [47–50], supports our finding that the antihypertrophic actions of CardAPs also occurred in an NO‐dependent manner. The IL‐10 dependency of CardAPs’ antihypertrophic actions is corroborated by the finding that IL‐10 exerts antihypertrophic effects [51], which are reflected in IL‐10’s anti‐inflammatory potential and its inhibitory effect on ERK signaling in cardiomyocytes [52].…”

Section: Discussionmentioning

confidence: 96%

Human Endomyocardial Biopsy Specimen-Derived Stromal Cells Modulate Angiotensin II-Induced Cardiac Remodeling

Miteva

Linthout

Pappritz

et al. 2016

Stem Cells Translational Medicine

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Cardiac-derived adherent proliferating cells (CardAPs) are cells derived from human endomyocardial biopsy specimens; they share several properties with mesenchymal stromal cells. The aims of this study were to evaluate whether intramyocardial injection of CardAPs modulates cardiac fibrosis and hypertrophy in a mouse model of angiotensin II (Ang II)-induced systolic heart failure and to analyze underlying mechanisms. Intramyocardial application of 200,000 CardAPs improved left ventricular function. This was paralleled by a decline in left ventricular remodeling, as indicated by a reduction in cardiac fibrosis and hypertrophy. CardAPs reduced the ratio of the left ventricle to body weight and cardiac myosin expression (heavy chain), and decreased the Ang II-induced phosphorylation state of the cardiomyocyte hypertrophy mediators Akt, extracellular-signal regulated kinase (ERK) 1, and ERK2. In accordance with the antifibrotic and antihypertrophic effects of CardAPs shown in vivo, CardAP supplementation with cardiac fibroblasts decreased the Ang II-induced reactive oxygen species production, a-SMA expression, fibroblast proliferation, and collagen production. Coculture of CardAPs with HL-1 cardiomyocytes downregulated the Ang II-induced expression of myosin in HL-1. All antifibrotic and antihypertrophic features of CardAPs were mediated in a nitric oxide-and interleukin (IL)-10-dependent manner. Moreover, CardAPs induced a systemic immunomodulation, as indicated by a decrease in the activity of splenic mononuclear cells and an increase in splenic CD4CD25FoxP3, CD4-IL-10, and CD8-IL-10 T-regulatory cells in Ang II mice. Concomitantly, splenocytes from Ang II CardAPs mice induced less collagen in fibroblasts compared with splenocytes from Ang II mice. We conclude that CardAPs improve Ang II-induced cardiac remodeling involving antifibrotic and antihypertrophic effects via paracrine actions and immunomodulatory properties. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1707-1718 SIGNIFICANCEDespite effective pharmacological treatment with angiotensin II type I receptor antagonists or angiotensin II-converting enzyme inhibitors, morbidity and mortality associated with heart failure are still substantial, prompting the search of novel therapeutic strategies. There is accumulating evidence supporting the use of cell therapy for cardiac repair. This study demonstrates that cells derived from human endomyocardial biopsies, cardiac-derived adherent proliferating cells (CardAPs), have the potential to reduce angiotensin II-induced cardiac remodeling and improve left ventricular function in angiotensin II mice. The mechanism involves antifibrotic and antihypertrophic effects via paracrine actions and immunomodulatory properties. These findings support the potential of CardAPs for the treatment of heart failure.

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IL-10 Inhibits the NF-κB and ERK/MAPK-Mediated Production of Pro-Inflammatory Mediators by Up-Regulation of SOCS-3 in Trypanosoma cruzi-Infected Cardiomyocytes

Cited by 65 publications

References 48 publications

Interleukin‐10 negatively modulates extracellular signal‐regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion

Interleukin‐10 negatively modulates extracellular signal‐regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion

Viral IL-10 down-regulates the “MHC-I antigen processing operon” through the NF-κB signaling pathway in nasopharyngeal carcinoma cells

Human Endomyocardial Biopsy Specimen-Derived Stromal Cells Modulate Angiotensin II-Induced Cardiac Remodeling

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