EPO modified MSCs can inhibit asthmatic airway remodeling in an animal model.

There was no effective measures can be obtained at present to reverse or prevent airway remodeling. We investigated the therapeutic effect of Erythropoietin (EPO) gene modified mesenchymal stem cells (MSCs) on asthmatic airway remodeling and the possible underlied molecular mechanisms. EPO gene was transfected into MSCs via lentivirus vector. The transfected cells (EPO-MSCs) were identified by flow cytometry and the EPO secreting function was detected by PCR and Western blot. MSCs or EPO-MSCs were administrated to albumin (OVA)-induced chronic asthmatic mouse model via tail veins. The asthmatic phenotype was analyzed. Number of cells in bronchoalveolar lavage fluid (BALF) was counted using a hemocytometer. Histological findings of airways were evaluated by microscopic examination. The concentrations of interleukin 4(IL-4), interleukin 5(IL-5), and interleukin 13(IL-13) in lung homogenate were determined by ELISA. The activation state of transforming growth factor-ß 1 (TGF-ß1), Transforming growth factor beta-activated kinase 1 (TAK1), and p38 Mitogen Activated Protein Kinase (p38MAPK) signaling was detected by Real-Time PCR and Western blotting. EPO-MSCs were successfully constructed. EPO-MSCs showed a more potently suppressive effect on local asthmatic airway inflammation and the level of IL-4, IL-5, and IL-13 in lung tissue than MSCs. Moreover, the numbers of goblet cells, the thicknesses of smooth muscle layer, collagen density, percentage of proliferating cell nuclear antigen positive (PCNA+ ) mesenchymal cells, and von Willebrand factor positive(vWF+ ) vessels were also significantly inhibited by EPO-MSCs. Furthermore, EPO-MSCs could downregulate the expression of TGF-ß1, TAK1, and p38MAPK in lung tissue both in mRNA level and in protein level. EPO gene modified MSCs may more efficiently attenuate asthmatic airway remodeling, which maybe related with the downregulation of TGF-ß1-TAK1-p38MAPK pathway activity.

Glutamine supplementation attenuates intestinal apoptosis by inducing heat shock protein 70 in heatstroke rats.

BACKGROUND: Heatstroke is the most hazardous heat-related illness and has a high fatality rate. We investigated whether glutamine supplementation could have a protective effect on heatstroke rats. METHODS: Twenty-five 12-week-old male Wistar rats (weight 305±16 g) were randomly divided into a control group (n=5), heatstroke (HS) group (n=10), and heatstroke+glutamine (HSG) group (n=10). Seven days before heat exposure, glutamine (0.4 g/[kg·d]) was administered to the rats in the HSG group by gavage every day. Three hours after heat exposure, serum samples were collected to detect white blood cells, coagulation indicators, blood biochemical indicators, and inflammatory cytokines in the rats. The small intestine tissue was stained to analyze pathological structural changes and apoptosis. Finally, immunohistochemistry and Western blotting were used to analyze the expression levels of heat shock protein 70 (HSP70). Multiple comparisons were analyzed by using one-way analysis of variance, and the Bonferroni test was conducted for the post hoc comparisons. RESULTS: After heat exposure, the core temperature of the HS group (40.65±0.31 °C) was higher than the criterion of heatstroke, whereas the core temperature of the HSG group (39.45±0.14 °C) was lower than the criterion. Glutamine supplementation restored the increased white blood cells, coagulation indicators, blood biochemical indicators, and inflammatory cytokines that were induced by heatstroke to normal levels. The intestinal mucosa was injured, and the structure of tight junctions was damaged in the HS group; however, the structure of intestinal mucosal epithelial cells was stable in the HSG group. Glutamine supplementation alleviated intestinal apoptosis and up-regulated HSP70 expression. CONCLUSION: Glutamine supplementation may alleviate intestinal apoptosis by inducing the expression of HSP70 and have a protective effect on heatstroke rats.

Therapeutic efficacy of a co-blockade of IL-13 and IL-25 on airway inflammation and remodeling in a mouse model of asthma.

Repeated airway inflammation and unremitting remodeling provoke irreversible pulmonary dysfunction and resistance to current drugs in patients with chronic bronchial asthma. Interleukin (IL)-13 and IL-25 play an important role in airway inflammation and remodeling in asthma. We aimed to investigate whether co-inhibiting IL-13 and IL-25 can effectively down-regulate allergen-induced airway inflammation and remodeling in mice. Mice with asthma induced by chronic exposure to ovalbumin (OVA) were given soluble IL-13 receptor α2 (sIL-13R) or soluble IL-25 receptor (sIL-25R) protein alone and in combination to neutralize the bioactivity of IL-13 and IL-25, and relevant airway inflammation and remodeling experiments were performed. We found that the co-blockade of IL-13 and IL-25 with sIL-13R and sIL-25R was more effective than either agent alone at decreasing inflammatory cell infiltration, airway hyperresponsiveness (AhR) and airway remodeling including mucus production, extracellular collagen deposition, smooth muscle cell hyperplasia and angiogenesis in mice exposed to OVA. These results suggest that the combined inhibition of IL-13 and IL-25 may provide a novel therapeutic strategy for asthma, especially for patients who are resistant to current treatments.