Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-α on the endothelium of murine aorta

Abstract

TNF-α is a proinflammatory cytokine and is an important mediator of maternal endothelial dysfunction leading to preeclampsia. In this study, we tested whether IL-10 protects against TNF-α-induced endothelial dysfunction in murine aorta. In in vitro experiments, aortic rings of C57BL/6 female mice were incubated in Dulbecco's modified Eagle's medium in the presence of either vehicle (distilled H(2)O), TNF-α (4 nmol/l), or recombinant mouse IL-10 (300 ng/ml) or in the presence of both TNF-α and IL-10 for 22 h at 37°C. In in vivo experiments C57BL6/IL-10 knockout female mice were treated with saline or TNF-α (220 ng·kg(-1)·day(-1)) for 14 days. Aortic rings were isolated from in vitro and in vivo experiments and mounted in a wire myograph (Danish Myotech) and stretched to a tension of 5 mN. Endothelium-dependent relaxation was assessed by constructing cumulative concentration-response curves to acetylcholine (ACh, 0.001-10 μmol/l) during phenylephrine (10 μmol/l)-induced contraction. As a result, overnight exposure of aortic rings to TNF-α resulted in significant blunted maximal relaxing responses (E(max)) to ACh compared with untreated rings (22 ± 4 vs. 82 ± 3%, respectively). IL-10 knockout mice treated with TNF-α showed significant impairment in ACh responses (E(max)) compared with C57BL/6 mice treated with TNF-α (51 ± 3 vs. 72 ± 3%, respectively). Western blot analysis showed that endothelial nitric oxide synthase (eNOS) expression was reduced by TNF-α in in vitro and in vivo experiments, whereas IL-10 restored the eNOS expression. In conclusion, the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation caused by TNF-α by protecting eNOS expression.

Akt1-Mediated Fast/Glycolytic Skeletal Muscle Growth Attenuates Renal Damage in Experimental Kidney Disease

“…18,43 In the UUO model, we found that myogenic activation of Akt upregulated serum levels of stromal cell-derived factor-1, IL-10, and IL-17, which are known to activate eNOS. 44,45 Further studies will be required to determine whether these factors are involved in renal eNOS activation and renoprotective properties of Akt1-mediated skeletal muscle growth.…”

Effect of Interleukin-10 and Laminar Shear Stress on Endothelial Nitric Oxide Synthase and Nitric Oxide in African American Human Umbilical Vein Endothelial Cells

“…In a study conducted on mice, the authors reported that IL-10 exerted its antiinflammatory influence by inhibiting the in vivo and in vitro adverse effects of TNF-α on the endothelium of the murine aorta by restoring the eNOS IL-10 and LSS in African American HUVECs -Babbitt et al protein expression that was reduced by TNF-α. 15 This study also showed that IL-10 without the presence of TNF-α had no effect on eNOS expression. 15 An additional study was conducted on HUVECs pre-incubated with TNF-α, and it was demonstrated that eNOS protein expression and NO production were increased in the cells subsequent to incubation with IL-10.…”

“…15 This study also showed that IL-10 without the presence of TNF-α had no effect on eNOS expression. 15 An additional study was conducted on HUVECs pre-incubated with TNF-α, and it was demonstrated that eNOS protein expression and NO production were increased in the cells subsequent to incubation with IL-10. 18 The authors concluded that in the presence of a pro-inflammatory stimulus, increased eNOS protein expression was mediated by the anti-inflammatory effect of IL-10.…”

“…16,17 Studies have also demonstrated that IL-10 is contributory in the up-regulation of endothelial nitric oxide synthase (eNOS) and subsequent bioavailability of nitric oxide (NO), a well-documented facilitator of vascular dilation that is critical for normal endothelial function. 15 Background: African Americans have a predisposition to heightened systemic inflammation and a high prevalence of hypertension.…”

Protection of mice against lipopolysaccharide-induced endotoxic shock by pinocembrin is correlated with regulation of cytokine secretion

“…(Guyon et al, 2008). Studies have also reported that IL-10 plays an essential role in the suppression of the production of pro-inflammatory cytokines like TNFa (Dhingra et al, 2009) by inhibiting NF-B activity in purified T-lymphocytes (Zemse et al, 2010).…”