miR-29b Reverses T helper 1 cells/T helper 2 cells Imbalance and Alleviates Airway Eosinophils Recruitment in OVA-Induced Murine Asthma by Targeting Inducible Co-Stimulator.

Asthma is a complex chronic disease and the pathogenesis is still not entirely clear. In this study, we aimed to clarify the role and mechanism of miR-29b in the development of asthma. We observed that miR-29b levels were decreased in the lung and spleen of OVA-induced asthmatic mice. Reverse transcription-quantitative polymerase chain reaction and flow cytometry demonstrated that the inducible co-stimulator (ICOS) expression at mRNA and protein levels was elevated in the lung of asthmatic mice, and miR-29b expression in the lung of asthmatic mice was negatively associated with ICOS mRNA levels by Pearson Correlation analysis. Additional, flow cytometry showed that the percentage of CD4+ICOS+ T cells in the lung and spleen was regulated by miR-29b, and dual luciferase reporter assay confirmed ICOS was a target gene of miR-29b. Furthermore, miR-29b overexpression in asthmatic mice was induced with miR-29b agomir by intranasal administration; miR-29b alleviated total inflammatory cell infiltration and CCL24 levels, decreased IL-5 levels in bronchoalveolar lavage fluid and serum, and upregulated IFN-γ expression in serum. This study demonstrates that miR-29b targets ICOS, thereby reverses the imbalance of T helper 1 cells (Th1)/Th2 responses and decreases eosinophils recruitment in the airway, which are key features of allergic airway inflammation. Therefore, miR-29b might be an attractive candidate target for asthma treatment.

Mast cell degranulation impairs pneumococcus clearance in mice via IL-6 dependent and TNF-α independent mechanisms.

BACKGROUND: Mast cells participate in immune responses by releasing potent immune system modifiers via degranulation. Due to currently reported controversial roles of mast cells in Streptococcus pneumoniae infections, this study aimed to determine the role and mechanism of mast cells in clearing S. pneumoniae in mice. METHODS: In vivo mouse model of mast cell degranulation established by administration of C48/80 was evaluated for the influences of mast cell degranulation on bacterial colonization and inflammation. In vitro model was established to observe the influences of mast cell degranulation on phagocytic and bactericidal functions of neutrophils and macrophages. IL-6 null and TNF-α null mice on the C57BL/6 background were used to investigate the effects of inflammatory factors released by mast cell degranulation on bacterial clearance. RESULTS: Mast cell degranulation increased IL-6 and TNF-α levels and immune cell numbers in nasal lavage fluid, and inhibited the bactericidal function of macrophages and neutrophils in vitro. It decreased the number of neutrophils and macrophages recruited to respiratory tract after S. pneumoniae challenge and inhibited the clearance of S. pneumoniae in mice. After pretreatment with C48/80, S. pneumoniae loads were significantly lower in IL-6 null mice than in wild type mice, while no differences were observed between TNF-α null and wild type mice. CONCLUSIONS: Mast cell degranulation can cause inflammation and impair immune cell recruitment to respiratory tract after S. pneumoniae challenge. Products of mast cell degranulation including IL-6 decreased the bactericidal function of neutrophils and macrophages. Through these mechanisms, mast cell degranulation inhibited clearance of S. pneumoniae in mice.

Progranulin Promotes Bleomycin-Induced Skin Sclerosis by Enhancing Transforming Growth Factor-ß/Smad3 Signaling through Up-Regulation of Transforming Growth Factor-ß Type I Receptor.

Progranulin (PGRN) is an autocrine growth factor with numerous physiological and pathologic roles. Previous reports demonstrated PGRN could increase dermal fibroblasts in wound healing and activate cancer-associated fibroblasts in some cancers. Because systemic sclerosis (SSc) is a prototypical fibrosis-related disorder, here, the aim was to clarify the role and mechanism of PGRN in bleomycin (BLM)-induced model of SSc for the first time. It was observed that the serum PGRN levels were increased in SSc patients compared with healthy controls. Immunohistology and quantitative RT-PCR demonstrated that PGRN was also elevated in the lesion from the mice model of BLM-induced dermal fibrosis. In addition, in BLM-treated mice, PGRN deficiency not only attenuated dermal fibrosis but also decreased the differentiation of myofibroblasts. The reduced progression of skin sclerosis in PGRN-deficient mice was associated with down-regulation of transforming growth factor (TGF)-ß receptor I (TßR I) and decreased level of phosphorylated Smad3, with correspondingly impaired expression of its downstream target gene connective tissue growth factor (CTGF) in skin lesion. In contrast, exogenous PGRN significantly increased the level of TßR I and phosphorylated Smad3 in cultured mouse fibroblasts. This study demonstrates that PGRN plays a promoting role in the development of dermal fibrosis through the activation of the TGF-ß/Smad3 signaling via up-regulation of TßR I. PGRN may be a new therapeutic target in SSc.

The patterns of Cd-binding proteins in rice and wheat seed and their stability.

The protein-binding forms of cadmium in polluted rice and wheat seeds and their stability were investigated using the methods of Sephadex chromatography. Three absorption peaks (F-I, F-II and F-III) were identified in Tris-HCl extraction of rice and wheat on Sephadex G 75. The Cd in the protein extracts from rice and wheat seeds was distributed mainly in the fractions of F-I and F-III. The apparent molecular weights of Cd-binding proteins for F-I and F-III were 54.5 and 5.5 KD, respectively. The components of amino acid for the protein bound with heavy metals were different. There were high contents of glutamic acid, cysteine, valine, isoleucine, leucine and tyrosine in the protein extracts of rice and wheat. After cooking, the Cd-binding proteins were destroyed. High molecular weight protein-binding form (54.5 KD) was broken into low molecular weight complex (5.5 KD) or tiny peptide chain. Simultaneously, Cd bound with protein was released, or mainly bound with protein of smaller molecular size. Enzyme treatment (pepsin and trypsin) also caused a destruction of Cd binding protein and a change in the distribution of Cd in the eluent. The concentrations of Cd in the elution of first and third peak decreased markedly, and the Cd distribution was observed in the elution after third peak (F-III).