[Show abstract][Hide abstract] ABSTRACT: P2X7 receptors have been involved in inflammatory and immunological responses, and their activation modulates pro-inflammatory cytokines production by LPS-challenged macrophages.
To determine the role of P2X7R in LPS-induced acute lung injury in mice.
Wild-type (C57BL/6) and P2X7 knockout mice received intratracheal injection of saline or Escherichia coli LPS (60 μg). After 24h, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage was performed, and lungs were harvested for measurement of morphometry, fibers content, inflammatory cells and cytokine expression by histochemistry and immunohistochemistry.
Compared with saline, LPS increased lung mechanical parameters, mast cell, collagen and fibronectin deposition in lung parenchyma, as well as nitric oxide and lactate dehydrogenase release into bronchoalveolar fluid in wild-type, but not in P2X7R knockout mice. Alveolar collapse, lung influx of polymorphonuclear and CD14(+) cells, as well as TGF-β, MMP-2, and IL-1β release were higher in wild-type than knockout LPS-challenged mice, while MMP-9 release where similar between the two genotypes. LPS increased macrophage immunoreactivity in lung tissue in both genotypes, but macrophages were not activated in the P2X7R knockout mice. Furthermore, LPS administration increased P2X7R immunoexpression in lung parenchyma in wild-type mice, and TLR4 in both wild-type and P2X7R knockout mice.
P2X7 receptors are implicated in the pathophysiology of LPS-induced lung injury, modulating lung inflammatory and functional changes.
[Show abstract][Hide abstract] ABSTRACT: Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-kappaB (NF-kappaB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 microg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (DeltaP1) and viscoelastic (DeltaP2) pressures, static elastance (E(st)), and viscoelastic component of elastance (DeltaE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-alpha was determined by ELISA. Lung tissue expression of NF-kappaB was determined by EMSA. DeltaP1, DeltaP2, E(st), and DeltaE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-alpha levels and NF-kappaB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.
No preview · Article · Apr 2010 · Journal of Applied Physiology
[Show abstract][Hide abstract] ABSTRACT: Short-term cigarette smoke exposure has been associated with acute lung inflammation (ALI) and oxidative damage. We studied mate tea (Ilex paraguariensis infusion) as a possible nutritional resource for ALI.
C57BL/6 mice (n = 30) were administered with mate tea orally (150 mg/kg, CSMO), mate tea intraperitonially (150 mg/kg, CSMIP), or the vehicle (CS) and then exposed to cigarette smoke for 5 d (six cigarettes per day). The control group was sham-smoked (n = 30). One day after the final exposure, mice were sacrificed. Bronchoalveolar lavages were performed and lungs removed for biochemical (lung homogenates) and histologic analyses.
Mate tea reduced the increase of alveolar macrophages and neutrophils in bronchoalveolar lavages (cells x 10(3)/mL) of the CSMO (214.3 +/- 21.4 and 12.2 +/- 4.9) and CSMIP (248.3 +/- 11.1 and 12.1 +/- 2.3) groups compared with the CS group (425.9 +/- 28.1 and 140.5 +/- 20.1). Mate tea reduced lipid peroxidation (the control group was considered 100%) and tumor necrosis factor-alpha (picograms per milliliter) in the CSMO group (61.3 +/- 11.3 and 185.3 +/- 21.8) compared with the CS group (150.0 +/- 18.1 and 242.3 +/- 13.2). Matrix metalloprotease-9 activity was higher in the CS group and lower in the CSMO group. Oxidative and inflammatory markers in the CSMO group were not different from those in the control group.
These data imply a potential antioxidant role for mate tea on ALI. Further studies are needed to determine such mechanisms and to explore its potential as an anti-inflammatory and nutritional resource in lung damaged by cigarette smoke exposure.
[Show abstract][Hide abstract] ABSTRACT: The mechanisms involved in the mitogenic effect of lectins are not fully understood and are thought to involve a cascade of intracellular signals related to T cell receptor activation. This study shows that frutalin, the alpha-D-galactose-binding lectin from Artocarpus incisa seeds, is a potent mitogenic activator of human lymphocytes. This effect is inhibited by D-galactose and PI3K inhibitors, and is accompanied by an increase in IL-2 receptor expression and by a PI3K-dependent IL-2 gene expression and IL-2 protein synthesis. Frutalin also induces Akt-phosphorylation and activates NF-kappaB, inducing its translocation from the cytosol to the nucleus. Both effects are blocked in the presence of D-galactose or by PI3K inhibitors. In summary, frutalin, interacting with alpha-D-galactose, activates signaling pathways related to TCR, and thereby triggers PI3K/Akt and NF-kappaB pathway, which modulates T cell proliferation, IL-2 synthesis and IL-2R expression. Frutalin might be a useful tool to study intracellular mechanisms following T cell activation that link upstream signaling pathways to downstream events.
No preview · Article · Apr 2006 · International Immunopharmacology
[Show abstract][Hide abstract] ABSTRACT: Several lectin-like molecules have been shown as potent activators of leukocytes. Galactose-binding lectins are of special interest since they could interact with several endogenous molecules involved in the innate and specific immune responses. The effects of Frutalin (FTL), an alpha-D-galactose (Gal)-binding plant lectin, on the modulation of neutrophil (PMN) functions were investigated. FTL induced a dose-dependent PMN migration in mice pleural cavity. Moreover, FTL was also a potent direct chemotactic for human PMN, in vitro, and triggered oxidative burst in these cells. These effects were accompanied by a rearrangement of the actin cytoskeleton dynamic, activation of tyrosine kinase (TK) pathways, increase in focal adhesion kinase (FAK) phosphorylation, and its subsequent association to phosphoinositide3-kinase (PI3K). All those effects were inhibited in the presence of Gal, suggesting specific carbohydrate recognition for FTL effects. The activations of TK and PI3K pathways are essential events for FTL-induced chemotaxis, since inhibitors of these pathways, genistein and LY294002, inhibited neutrophil migration in vitro. The data indicate that sugar-protein interactions between a soluble lectin and galacto-components on neutrophil surface trigger the TK pathway, inducing FAK and PI3K activation, interfering with cell motility and oxidative response.
No preview · Article · Nov 2005 · Toxicology and Applied Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Strains of mice obtained by genetic selection to extremes of phenotype for susceptibility or resistance to oral tolerance were investigated for possible genetic correlations with acute inflammatory response using different models of inflammation. The results show a strong genetic association.
No preview · Article · Jan 2005 · Annals of the New York Academy of Sciences