Differential expression and function of breast regression protein 39 (BRP-39) in murine models of subacute cigarette smoke exposure and allergic airway inflammation

Background

While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM), is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation.

Methods

CD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO) mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation.

Results

Cigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke.

Conclusions

These data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1 inflammatory pathway.     

Cupressaceae pollen in the atmosphere of Ascoli Piceno (Central Italy) and sensitization of allergic subjects

The aim of this work is to study the incidence of pollinosis in the Health District of Ascoli Piceno, Central Italy (U.S.L.24). this being an underestimated pathology from the clinical point of view and also as a result of the recent introduction of this taxa in the National Aeroallergen Network. Since 1990, 5055 patients of both sexes with respiratory symptomatology of suspected IgE mediated aetiology have been examined in our Centre with the Skin Prick Test (SPT) using allergen panels including Cypress; 171 (3.38%) patients were found to be positive to this allergen. These results show that the subjects with symptoms in the period January–March in most cases have a sensitization toCupressus pollen and new studies will evaluate the possibility of specific immunotherapy.     

Dietary conjugated linoleic acid does not adversely affect bone mass in obese fa/fa or lean Zucker rats

Conjugated linoleic acid (CLA) elevates body ash in healthy animals. The objective of the present study was to determine if single or mixed CLA isomers improve bone mass in an obese and hyperinsulinemic state. Male (n = 120) lean and obese fa/fa Zucker rats (age, 6 weeks) were randomized to 8 weeks on a control diet or to 0.4% (w/w) cis-9, trans-11 CLA (Group 1); 0.4% (w/w) trans-10, cis-12 CLA (Group 2); 0.4% (w/w) cis-9, trans-11 CLA and 0.4% (w/w) trans-10, cis-12 CLA (Group 3); 0.4% (w/w) cis-9, trans-11 CLA, 0.4% (w/w) trans-10, cis-12 CLA, and traces of other CLA isomers (Group 4); and 0.4% (w/w) cis-9, trans-11 CLA, 0.4% (w/w) trans-10, cis-12 CLA, and 0.3% (w/w) other CLA isomers (Group 5). Bone area (BA), bone mineral content (BMC), and bone mineral density (BMD) of the whole body, spine, and femur were measured at baseline (6 weeks) and at 14 weeks of age. Effects of genotype, diet, and genotype x diet interactions were assessed using factorial analysis of variance. At 6 and 14 weeks, whole-body BA and BMC were lower in lean rats compared with fa/fa rats. Similarly, at 14 weeks, fa/fa rats had a higher spine and femur BMD despite a lower femur weight. The fa/fa rats in Groups 4 and 5 had higher adjusted whole-body BMC compared with Group 3, but not with Group 1, Group 2, or the control. In lean rats, Group 3 had a greater adjusted whole-body BMC than Groups 1 and 2, but not Group 4, Group 5, or the control. Thus, commercially available CLA mixtures and single CLA isomers do not affect bone mass in a hyperinsulinemic, obese state.     

Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying

Intestinal perfusion with carbohydrates inhibits gastric emptying via vagal and spinal capsaicin-sensitive afferent pathways. The aim of the present study was to determine the role of 1) 5-hydroxytryptamine (5-HT)(3) receptors (5-HT(3)R) in mediating glucose-induced inhibition of gastric emptying and 2) 5-HT(3)R expression in vagal and spinal afferents in innervating the duodenum. In awake rats fitted with gastric and duodenal cannulas, perfusion of the duodenum with glucose (50 and 100 mg) inhibited gastric emptying. Intestinal perfusion of mannitol inhibited gastric emptying only at the highest concentration (990 mosm/kgH(2)O). Pretreatment with the 5-HT(3)R antagonist tropisetron abolished both glucose- and mannitol-induced inhibition of gastric emptying. Retrograde labeling of visceral afferents by injection of dextran-conjugated Texas Red into the duodenal wall was used to identify extrinsic primary afferents. Immunoreactivity for 5-HT(3)R, visualized with an antibody directed to the COOH terminus of the rat 5-HT(3)R, was found in >80% of duodenal vagal and spinal afferents. These results show that duodenal extrinsic afferents express 5-HT(3)R and that the receptor mediates specific glucose-induced inhibition of gastric emptying. These findings support the hypothesis that enterochromaffin cells in the intestinal mucosa release 5-HT in response to glucose, which activates 5-HT(3)R on afferent nerve terminals to evoke reflex changes in gastric motility. The primary glucose sensors of the intestine may be mucosal enterochromaffin cells.     

Hydraulic Lift in Cork Oak Trees in a Savannah-Type Mediterranean Ecosystem and its Contribution to the Local Water Balance

The aim of this study was to identify the sources and depth of water uptake by 15-years old Quercus suber L. trees in southern Portugal under a Mediterranean climate, measuring δ¹⁸O and δD in the soil–plant-atmosphere continuum. Evidence for hydraulic lift was substantiated by the daily fluctuations observed in Ψ_s at 0.4 and 1 m depth and supported by similar δ¹⁸O values found in tree xylem sap, soil water in the rhizosphere and groundwater. From 0.25 m down to a depth of 1 m, δD trends differed according to vegetation type, showing a more depleted value in soil water collected under the evergreen trees (−47‰) than under dead grasses (−35‰). The hypothesis of a fractionation process occurring in the soil due to diffusion of water vapour in the dry soil is proposed to explain the more depleted soil δD signature observed under trees. Hydraulically lifted water was estimated to account for 17–81% of the water used during the following day by tree transpiration at the peak of the drought season, i.e., 0.1–14 L tree⁻¹ day⁻¹. Significant relationships found between xylem sap isotopic composition and leaf water potential in early September emphasized the positive impact of the redistribution of groundwater in the rhizosphere on tree water status.     

Use of plants by Myzus persicae in agroecosystems: Potential applications in conservation biological control

Myzus persicae (Sulzer) is a highly polyphagous aphid species that attacks several economically important crop plants. Here, trophic webs involving M. persicae, its host plants and its parasitoids were described and quantified in wheat, oat and alfalfa agroecosystems from central Argentina, with special emphasis on the sub-habitats where interactions occur: crops and adjacent field margins. Three fields cultivated with each crop species and their margins were sampled during three years; aphid abundance and mummification percentage were compared among crop plants and the diverse natural vegetation in the borders. Interactions were described using a quantitative food web approach, and abundance and mummification percentage e data were analysed using a generalized linear model. Four plant species present in the borders (Capsella bursa-pastori, Rapistrum sp., Melilotus sp. and Trifolium repens) hosted M. persicae and its parasitoids. The alfalfa agroecosystem produced a significantly higher number of aphids than oat and wheat; however, in all cases, crops and borders sustained similar aphid abundance. A total of six Aphidiinae species attacked M. persicae, with no significant differences in the richness of parasitoid species between the borders and the crops, but with significant differences in parasitoid abundance, being higher in the crops. Mummification percentage were higher in crops than in the borders, with Lysiphlebus testaceipes, Aphidius colemani and A. ervi being the most abundant species. Almost 70% of M. persicae individuals were collected from fields borders, which highlights the importance of including these sites in studies of trophic interactions in crop fields.     

Bindarit Inhibits Human Coronary Artery Smooth Muscle Cell Proliferation,Migration and Phenotypic Switching

Bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs) synthesis, reduces neointimal formation in animal models of vascular injury and recently has been shown to inhibit in-stent late loss in a placebo-controlled phase II clinical trial. However, the mechanisms underlying the efficacy of bindarit in controlling neointimal formation/restenosis have not been fully elucidated. Therefore, we investigated the effect of bindarit on human coronary smooth muscle cells activation, drawing attention to the phenotypic modulation process, focusing on contractile proteins expression as well as proliferation and migration. The expression of contractile proteins was evaluated by western blot analysis on cultured human coronary smooth muscle cells stimulated with TNF-α (30 ng/mL) or fetal bovine serum (5%). Bindarit (100–300 µM) reduced the embryonic form of smooth muscle myosin heavy chain while increased smooth muscle α-actin and calponin in both TNF-α- and fetal bovine serum-stimulated cells. These effects were associated with the inhibition of human coronary smooth muscle cell proliferation/migration and both MCP-1 and MCP-3 production. The effect of bindarit on smooth muscle cells phenotypic switching was confirmed in vivo in the rat balloon angioplasty model. Bindarit (200 mg/Kg/day) significantly reduced the expression of the embryonic form of smooth muscle myosin heavy chain, and increased smooth muscle α-actin and calponin in the rat carodid arteries subjected to endothelial denudation. Our results demonstrate that bindarit induces the differentiated state of human coronary smooth muscle cells, suggesting a novel underlying mechanisms by which this drug inhibits neointimal formation.