16 research outputs found
Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma
Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors participate in the coordination of the cell’s energy requirement and in the mitochondrial oxidative phosphorylation enzyme (OXPHOS) biosynthesis, affecting reactive oxygen species (ROS) generation and induction of apoptosis. Although activation of mtGR and mtER is known to trigger anti-inflammatory signals, little information exists on the presence of these receptors in lung tissue and their role in respiratory physiology and disease. Using a mouse model of allergic airway inflammation disease and applying confocal microscopy, subcellular fractionation, and Western blot analysis we showed mitochondrial localization of GRα and ERβ in lung tissue. Allergic airway inflammation caused reduction in mtGRα, mtERβ, and OXPHOS enzyme biosynthesis in lung cells mitochondria and particularly in bronchial epithelial cells mitochondria, which was accompanied by decrease in lung mitochondrial mass and induction of apoptosis. Confirmation and validation of the reduction of the mitochondrial receptors in lung epithelial cells in human asthma was achieved by analyzing autopsies from fatal asthma cases. The presence of the mitochondrial GRα and ERβ in lung tissue cells and especially their reduction in bronchial epithelial cells during allergic airway inflammation suggests a crucial role of these receptors in the regulation of mitochondrial function in asthma, implicating their involvement in the pathophysiology of the disease
Angiopoietin-1 protects against airway inflammation and hyperreactivity in asthma
Rationale: The angiopoietins (Ang) comprise a family of growth factors
mainly known for their role in blood vessel formation and remodeling.
The best-studied member, Ang-1, exhibits antiapoptotic and
antiinflammatory effects. Although the involvement of Ang-1 in
angiogenesis is well recognized, little information exists about its
role in respiratory physiology and disease. On the basis of its ability
to inhibit vascular permeability, adhesion molecule expression, and
cytokine production, we hypothesized that Ang-1 administration might
exert a protective role in asthma.
Objectives: To determine changes in the expression of Ang and to assess
the ability of Ang-1 to prevent the histologic, biochemical, and
functional changes observed in an animal model of asthma.
Methods: To test our hypothesis, a model of allergic airway disease that
develops after ovalbumin (OVA) sensitization and challenge was used.
Measurements and Main Results: Ang-1 expression was reduced at the mRNA
and protein levels in lung tissue of mice sensitized and challenged with
OVA, leading to reduced Tie2 phosphorylation. Intranasal Ang-1 treatment
prevented the OVA-induced eosinophilic lung infiltration, attenuated the
increase in IL-5 and IL-13, and reduced eotaxin and vascular cell
adhesion molecule 1 expression. These antiinflammatory actions of Ang-1
coincided with higher levels of I kappa B and decreased nuclear
factor-kappa B binding activity. More importantly, Ang-1 reversed the
OVA-induced increase in tissue resistance and elastance, improving lung
function.
Conclusions: We conclude that Ang-1 levels are decreased in asthma and
that administration of Ang-1 might be of therapeutic value because it
prevents the increased responsiveness of the airways to constrictors and
ameliorates inflammation
Effects of rehabilitative exercise on peripheral muscle TNFα, IL‐6, IGF‐I and MyoD expression in patients with COPD
Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation. This study investigated whether rehabilitative exercise training decreases the levels of systemic or local muscle inflammation or reverses the abnormalities associated with muscle deconditioning.
Methods: Fifteen patients with COPD (mean (SE) forced expiratory volume in 1 s 36 (4)% predicted) undertook high-intensity exercise training 3 days/week for 10 weeks. Before and after the training programme the concentration of tumour necrosis factor α (TNFα), interleukin-6 (IL-6) and C-reactive protein (CRP) in plasma was determined by ELISA, and vastus lateralis mRNA expression of TNFα, IL-6, total insulin-like growth factor-I (IGF-I) and its isoform mechanogrowth factor (MGF) and myogenic differentiation factor D (MyoD) were assessed by real-time PCR. Protein levels of TNFα, IGF-I and MyoD were measured by Western blotting.
Results: Rehabilitation improved peak exercise work rate by 10 (2%) (p = 0.004) and mean fibre cross-sectional area from 4061 (254) μm2 to 4581 (241) μm2 (p = 0.001). Plasma inflammatory mediators and vastus lateralis expression of TNFα and IL-6 were not significantly modified by training. In contrast, there was a significant increase in mRNA expression of IGF-I (by 67 (22)%; p = 0.044), MGF (by 67 (15)%; p = 0.002) and MyoD (by 116 (30)%; p = 0.001). The increase observed at the mRNA level was also seen at the protein level for IGF-I (by 72 (36)%; p = 0.046) and MyoD (by 67 (21)%; p = 0.012).
Conclusions: Pulmonary rehabilitation can induce peripheral muscle adaptations and modifications in factors regulating skeletal muscle hypertrophy and regeneration without decreasing the levels of systemic or local muscle inflammation
Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma
Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors
participate in the coordination of the cell’s energy requirement and in
the mitochondrial oxidative phosphorylation enzyme (OXPHOS)
biosynthesis, affecting reactive oxygen species (ROS) generation and
induction of apoptosis. Although activation of mtGR and mtER is known to
trigger anti-inflammatory signals, little information exists on the
presence of these receptors in lung tissue and their role in respiratory
physiology and disease. Using a mouse model of allergic airway
inflammation disease and applying confocal microscopy, subcellular
fractionation, and Western blot analysis we showed mitochondrial
localization of GR alpha and ER beta in lung tissue. Allergic airway
inflammation caused reduction in mtGR alpha, mtER beta, and OXPHOS
enzyme biosynthesis in lung cells mitochondria and particularly in
bronchial epithelial cells mitochondria, which was accompanied by
decrease in lung mitochondrial mass and induction of apoptosis.
Confirmation and validation of the reduction of the mitochondrial
receptors in lung epithelial cells in human asthma was achieved by
analyzing autopsies from fatal asthma cases. The presence of the
mitochondrial GR alpha and ER beta in lung tissue cells and especially
their reduction in bronchial epithelial cells during allergic airway
inflammation suggests a crucial role of these receptors in the
regulation of mitochondrial function in asthma, implicating their
involvement in the pathophysiology of the disease
Secreted phosphoprotein-1 directly provokes vascular leakage to foster malignant pleural effusion
Secreted phosphoprotein-1 (SPP1) promotes cancer cell survival and regulates tumor-associated angiogenesis and inflammation, both central to the pathogenesis of malignant pleural effusion (MPE). Here, we examined the impact of tumor- and host-derived SPP1 in MPE formation and explored the mechanisms by which the cytokine exerts its effects. We used a syngeneic murine model of lung adenocarcinoma-induced MPE. To dissect the effects of tumor- versus host-derived SPP1, we intrapleurally injected wild-type and SPP1-knockout C57/BL/6 mice with either wild-type or SPP1-deficient syngeneic lung cancer cells. We demonstrated that both tumor- and host-derived SPP1 promoted pleural fluid accumulation and tumor dissemination in a synergistic manner (P<0.001). SPP1 of host origin elicited macrophage recruitment into the cancer-affected pleural cavity and boosted tumor angiogenesis, whereas tumor-derived SPP1 curtailed cancer cell apoptosis in vivo. Moreover, the cytokine directly promoted vascular hyper-permeability independently of vascular endothelial growth factor. In addition, SPP1 of tumor and host origin differentially affected the expression of proinflammatory and angiogenic mediators in the tumor microenvironment. These results suggest that SPP1 of tumor and host origin impact distinct aspects of MPE pathobiology to synergistically promote pleural fluid formation and pleural tumor progression. SPP1 may present an attractive target of therapeutic interventions for patients with MPE