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Lin F.,Chongqing University | Song A.,Guangdong Provincial Institute of Sports Science | Wu J.,Chongqing University | Jiang X.,Chongqing University | And 6 more authors.
Molecular Medicine Reports | Year: 2013

A disintegrin and metalloproteinase 33 (ADAM33) has been identified as an asthma susceptibility gene; however, the role of ADAM33 in the pathogenesis and progression of asthma remains to be elucidated. As ADAM33 is predominantly expressed in airway smooth muscle cells (ASMCs), it is feasible to investigate whether ADAM33 protein expression is correlated with ASMC mechanics that are ultimately responsible for airway hyperresponsiveness in asthma. To determine this, Sprague Dawley rats were sensitized with ovalbumin (OVA) for up to 12 weeks to simulate asthma symptoms. Subsequently, ASMCs were isolated from the rats and cultured in vitro. The protein expression of ADAM33 and cytoskeletal proteins (including F-actin and vinculin), cell stiffness and contractility, as well as traction force were measured. The results demonstrated that compared with the non-sensitized rats, the protein expression of ADAM33 in ASMCs from the OVA-sensitized rats increased in a time-dependent manner, reaching a maximum level at 4 weeks of sensitization and gradually subsiding as OVA sensitization continued (P<0.001). The cell stiffness, traction force and expression of vinculin and F-actin changed similarly, resulting in a positive correlation with ADAM33 protein expression (Pearson's correlation coefficient, 0.864, 0.716, 0.774 and 0.662, respectively; P=0.1-0.3). The in vivo results of OVA-induced ADAM33 protein expression and its association with the mechanics of ASMCs suggested that ADAM33 is a mediator of ASMC dysfunction in asthma, and may provide a rationale for the therapeutic targeting of ADAM33 in the treatment of asthma. Source


Song A.,Changzhou University | Song A.,Guangdong Provincial Institute of Sports Science | Lin F.,Changzhou University | Li J.,Purdue University | And 4 more authors.
Inhalation Toxicology | Year: 2014

Sulfur dioxide (SO2) is a common air pollutant that triggers asthmatic symptoms, but its toxicological mechanisms are not fully understood. Specifically, it is unclear how SO2 in vivo affects airway smooth muscle (ASM) cells of which the mechanics is known to ultimately mediate airway hyperresponsiveness (AHR)-a hallmark feature of asthma. To this end, we investigated the effects of bisulfite/sulfite (1:3 M/M in neutral fluid to simulate the in vivo derivatives of inhaled SO2 in the airways), on the viability, migration, stiffness and contractility of ASM cells cultured in vitro. The results showed that bisulfite/sulfite consistently increased viability, migration, F-actin intensity and stiffness of ASM cells in similar fashion as concentration increasing from 10-4 to 10 -1mmol/L. However, bisulfite/sulfite increased the ASM cell contractility induced by KCl only at the concentration between 10-4 and 10-3mmol/L (p<0.05), while having no consistent effect on that induced by histamine. At the concentration of 100mmol/L, bisulfite/sulfite became acutely toxic to the ASM cells. Taken together, the data suggest that SO2 derivatives at low levels in vivo may directly increase the mass, stiffness and contractility of ASM cells, which may help understand the mechanism in which specific air pollutants contribute in vivo to the pathogenesis of asthma. © 2014 Informa Healthcare USA, Inc. Source


Wang L.,Jinan University | Wang L.,Guangdong Provincial Institute of Sports Science | Li C.,Jinan University | Lin Q.,Jinan University | And 6 more authors.
Acta Biochimica et Biophysica Sinica | Year: 2015

Cucurbitacin E (CucE), a triterpenoid isolated from Cucurbitaceae plants, has been shown to possess an anti-inflammatory or immunosuppressive activity in vitro and in vivo, yet the underlying mechanism has been incompletely understood. The aim of the present study was to explore its effect on cytokine expression and the underlying mechanism in human Jurkat T cells as a cellular model. The results showed that CucE significantly inhibited the production of interleukin-2, tumor necrosis factor- α, and interferon-γ in culture medium of cells treated with phorbol 12,13-dibutyrate (PDB) plus ionomycin (Ion). Furthermore, the mRNA levels of these cytokines in activated Jurkat T cells were also decreased upon CucE treatment, suggesting a potential modulatory effect on the critical signaling pathways for cytokine expression, including nuclear factor-κB (NF-κB) or mitogen-activated protein kinases (MAPKs). In support of its effect on the NF-κB signaling pathway, CucE decreased the phosphorylation levels of inhibitor of κB (IκB) and NF-κB/p65 in PDB + Ion-stimulated cells. Further supporting this, the nuclear translocation of NF-κB/p65 was significantly suppressed in response to PDB plus Ion stimulation in the presence of CucE. The phosphorylation of p38MAPK, c-Jun N-terminal kinase (JNK), and Erk1/2, however, was not decreased or slightly increased at some time points by CucE treatment. Collectively, these data suggest that CucE may exhibit immunosuppressive effect by attenuating critical cytokine expression through down-regulating the NF-κB signaling pathway. © The Author 2015. Source


Zhou J.-J.,Sun Yat Sen University | Chen R.-F.,Sun Yat Sen University | Deng X.-G.,Sun Yat Sen University | Zhou Y.,Sun Yat Sen University | And 8 more authors.
FEBS Letters | Year: 2014

HCV Core plays a role in the development of hepatocellular carcinoma. Aberrant expression of NANOG has been observed in many types of human malignancies. However, relationship between Core and NANOG has not been clarified. In this study, we found that Core is capable of up-regulating NANOG expression. Core-induced NANOG expression was accompanied by enforced expression of phosphorylated stat3 protein and was attenuated by inhibition of stat3 phosphorylation. ChIP showed that phosphorylated stat3 directly binds to the NANOG promoter. Core-induced NANOG expression resulted in enhanced cell growth and cell cycle progression. Knockdown of NANOG blocked the cell cycle at the G0/G1 phases and inhibited the cyclin D1 expression. Our findings provide a new insight into the mechanism of hepatocarcinogenesis by HCV infection. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Source


Liu K.-P.,Jinan University | Zhou D.,Jinan University | Ouyang D.-Y.,Jinan University | Xu L.-H.,Jinan University | And 4 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Autophagy is a conserved mechanism for controlling the degradation of misfolded proteins and damaged organelles in eukaryotes and can be induced by nutrient withdrawal, including serum starvation. Although differential acetylation of autophagy-related proteins has been reported to be involved in autophagic flux, the regulation of acetylated microtubule-associated protein 1 light chain 3 (LC3) is incompletely understood. In this study, we found that the acetylation levels of phosphotidylethanolamine (PE)-conjugated LC3B (LC3B-II), which is a critical component of double-membrane autophagosome, were profoundly decreased in HeLa cells upon autophagy induction by serum starvation. Pretreatment with lysosomal inhibitor chloroquine did not attenuate such deacetylation. Under normal culture medium, we observed increased levels of acetylated LC3B-II in cells treated with tubacin, a specific inhibitor of histone deacetylase 6 (HDAC6). However, tubacin only partially suppressed serum-starvation-induced LC3B-II deacetylation, suggesting that HDAC6 is not the only deacetylase acting on LC3B-II during serum-starvation-induced autophagy. Interestingly, tubacin-induced increase in LC3B-II acetylation was associated with p62/SQSTM1 accumulation upon serum starvation. HDAC6 knockdown did not influence autophagosome formation but resulted in impaired degradation of p62/SQSTM1 during serum starvation. Collectively, our data indicated that LC3B-II deacetylation, which was partly mediated by HDAC6, is involved in autophagic degradation during serum starvation. © 2013 Elsevier Inc. Source

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