Zhengxiang Liu

Opposing roles of IL-17A and IL-25 in the regulation of TSLP production in human nasal epithelial cells.

To cite this article: Xu G, Zhang L, Wang DY, Xu R, Liu Z, Han DM, Wang XD, Zuo KJ, Li HB. Opposing roles of IL‐17A and IL‐25 in the regulation of TSLP production in human nasal epithelial cells. Allergy 2010; 65: 581–589.

Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patterns

The remodeling patterns in different types of chronic rhinosinusitis (CRS) have rarely been compared, particularly the difference between eosinophilic and noneosinophilic CRS with nasal polyps (CRSwNP). Moreover, whether there is a link between remodeling and inflammation remains controversial.

Interaction of thymic stromal lymphopoietin, IL-33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps

Thymic stromal lymphopoietin (TSLP), IL‐25, and IL‐33 system contribute to the initiation and development of Th2 responses. This study aimed to explore the involvement of TSLP, IL‐25, IL‐33, and their receptors in type 2 T‐helper (Th) responses in chronic rhinosinusitis with nasal polyps (CRSwNPs) and their cross‐regulation in human nasal epithelial cells (HNECs).

Estradiol improves cardiovascular function through up-regulation of SOD2 on vascular wall

Epidemiological studies have shown that estrogens have protective effects in cardiovascular diseases, even though the results from human clinical trials remain controversial, while most of the animal experiments confirmed this effect, but the detailed mechanism remains unclear. In this study, we found that estradiol (E2) treatment significantly increases the expression of mitochondrial superoxide dismutase (SOD2) in mice and in vitro in human aorta endothelial cells. Further investigation shows that E2 up-regulates SOD2 through tethering of estrogen receptor (ER) to Sp1 and the increased binding of Sp1 to GC-box on the SOD2 promoter, where ERα responses E2-mediated gene activation, and ERβ maintains basal gene expression level. The E2/ER-mediated SOD2 up-regulation results in minimized ROS generation, which highly favors healthy cardiovascular function. Gene therapy through lentivirus-carried endothelium-specific delivery to the vascular wall in high-fat diet (HFT) mice shows that the SOD2 expression in endothelial cells normalizes E2 deficiency-induced ROS generation with ameliorated mitochondrial dysfunction and vascular damage, while SOD2 knockdown worsens the problem despite the presence of E2, indicating that E2-induced SOD2 expression plays an important vasculoprotective role. To our knowledge, this is the first report for the mechanism by which E2 improves cardiovascular function through up-regulation of SOD2 in endothelial cells. In turn, this suggests a novel gene therapy through lentivirus-carried gene delivery to vascular wall for E2 deficiency-induced cardiovascular damage in postmenopausal women.

Th17 response and its regulation in inflammatory upper airway diseases

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two widely prevalent inflammatory diseases in the upper airways. T cell immunity has been suggested to play an important pathogenic role in many chronic inflammatory diseases including inflammatory upper airway diseases. Inappropriate CD4+ T cell responses, especially the dysregulation of the Th1/Th2 balance leading to excessive Th1 or Th2 cell activation, have been associated with allergic rhinitis and chronic rhinosinusitis. Nevertheless, recent studies suggest that IL‐17A and IL‐17A‐producing Th17 cell subset, a distinct pro‐inflammatory CD4+ T cell lineage, may also play an important role in the pathophysiology of inflammatory upper airway diseases. Th17 cells may promote both eosinophilic and neutrophilic inflammation in AR and CRS. In addition, a few, but accumulating evidence shows that the Th17 responses can be tightly regulated by endogenous and exogenous substances in the context of AR and CRS. This review discusses recent advances in our understanding of the expression and function of the Th17 response and its regulation in inflammatory upper airway diseases, and the perspective for future investigation and clinical utility.

Effect of ginsenoside Re on cardiomyocyte apoptosis and expression of Bcl-2/Bax gene after ischemia and reperfusion in rats

SummaryTo observe the effect of ginsenoside Re on cardiomyocyte apoptosis and Bcl-2/Bax gene expression after ischemia (30 min) and reperfusion (6 h) in rats and to elucidate the possible mechanisms of ginsenoside Re on inhibition of cardiomyocyte apoptosis, the ischemia/reperfusion heart model was established by ligating the left anterior descending branch of coronary artery in Wistar rats. The apoptotic cardiomyocytes were confirmed by transmission electron microscopy and counted byin situ nick end labeling (TUNEL) method and light microscopy. The mRNA and protein expression of Bcl-2 and Bax genes were studied byin situ hybridization and immunohistochemical staining. Mean optical density (OD) value of the positive fields of mRNA and protein expression was quantitatively examined by image analysis system. The results were as follows: (1) The apoptotic cardiomyocytes were found in ischemic fields in the ischemia/reperfusion group and weren’t observed in the sham-operation group by transmission electron microscopy; (2) The numbers of the apoptotic cells were 134.45±45.61/field in the ischemia/reperfusion group, and 90.66±19.22/field in the ginsenoside Re-treated group. The differences was significant between two groups (P<0.01); (3) Gene expression of Bcl-2 and Bax were increased significantly in the ischemia/reperfusion group and ginsenoside Re-treated group when compared with the sham-operation group. There was no significant difference in the gene expression of Bcl-2 between the ginsenoside Re-treated group and ischemia/reperfusion group (P>0.05), but gene expression of Bax was decreased significantly in the ginsenoside Re-treated group as compared with the ischemia/reperfusion group (P<0.01). The ratio of Bcl-2/Bax was increased significantly in the ginsenoside Re-treated group when compared with the ischemia/reperfusion group and sham-operation group. These findings suggest that myocardial ischemia-reperfusion can induce cardiomyocyte apoptosis, and ginsenoside Re can significantly inhibit cardiomyocyte apoptosis induced by ischemia-reperfusion in rats. It is concluded that ginsenoside Re inhibits cardiomyocyte apoptosis by inhibiting expression of pro-apoptotic Bax gene and raising the ratio of Bcl-2/Bax.

Role of tetraspanin CD151-α3/α6 integrin complex: Implication in angiogenesis CD151-integrin complex in angiogenesis.

Tetraspanin CD151 mainly associates with laminin-binding integrins and forms CD151-integrin complex. We previously reported that CD151 could be a potential target for angiogenesis, but the mechanisms involved are still unclear. This study investigated the role of CD151-integrin complex in angiogenesis and the signaling mechanisms involved. Here we showed that CD151 and CD151-AAA mutant were both well expressed at the protein level. CD151 gene transfer promoted angiogenesis and improved skin temperature of the lateral ischemic hindlimb, whereas CD151-AAA mutant abrogated the increase in capillary density and skin temperature. Further, CD151-AAA mutant failed to activate the FAK, ERK, PI3K/Akt/eNOS, and Rac1/Cdc42 signaling pathways. Moreover, CD151-AAA mutant was unavailable to promote bovine aortic endothelial cells (BAECs) proliferation and migration, in contrast to the effects of CD151. The results suggested that formation of CD151-integrin complex was likely to be a prerequisite for CD151-induced angiogenesis and signaling pathways.

CD151 promotes cancer cell metastasis via integrins α3β1 and α6β1 in vitro

CD151 is a member of the tetraspanin family that is implicated as a promoter of the tumor metastasis of malignant cells. Tetraspanins form membrane complexes with integrins. In the present study, we constructed a CD151-AAA mutant to assess the roles of Rac, cdc42 and phospho-Rac/cdc42 (P-Rac/cdc42) and the effects of CD151‑integrin complexes on the proliferation, migration and invasion of HepG2 cells. The pAAV-CD151 and pAAV‑CD151‑AAA mutant plasmids were constructed and used to transiently transfect HepG2 cells using the Qiagen Attractene transfection reagent. Following transfection, the expression of CD151 was determined by western blotting. A cell proliferation assay was performed using the cell counting kit-8 (CCK-8) method, cell migration was assessed by a cell wound-healing assay and cell invasion was evaluated in microchemotaxis chambers using FBS as the chemotactic stimulus. The potential involvement of various signaling pathways was explored using relevant antibodies. The association between CD151 and integrins was evaluated by immunoblotting analysis. We found that CD151 promoted cell proliferation, migration and chemotaxis and increased P-Rac/cdc42 activity. The CD151-AAA mutant had reduced cellular proliferation, migration and invasion compared with the CD151 mutant. Moreover, the CD151-AAA mutant abrogated the association between CD151 and integrins. These data suggest that CD151 forms complexes by interacting with integrins, particularly α3β1 and α6β1, and thereby affects the functioning of the HepG2 cells. The mechanism is possibly related to the Rac, cdc42 and P-Rac/cdc42 signaling pathways.

Diagnostic Power of Longitudinal Strain at Rest for the Detection of Obstructive Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus

Global longitudinal strain (GLS) measured by 2-D speckle-tracking echocardiography (2-D STE) at rest has been recognized as a sensitive parameter in the detection of significant coronary artery disease (CAD). However, the diagnostic power of 2-D STE in the detection of significant CAD in patients with diabetes mellitus is unknown. Two-dimensional STE features were studied in total of 143 consecutive patients who underwent echocardiography and coronary angiography. Left ventricular global and segmental peak systolic longitudinal strains (PSLSs) were quantified by speckle-tracking imaging. In the presence of obstructive CAD (defined as stenosis ≥75%), global PSLS was significantly lower in patients with diabetes mellitus than in patients without (16.65 ± 2.29% vs. 17.32 ± 2.27%, p < 0.05). Receiver operating characteristic analysis revealed that global PSLS could effectively detect obstructive CAD in patients without diabetes mellitus (cutoff value: -18.35%, sensitivity: 78.8%, specificity: 77.5%). However, global PSLS could detect obstructive CAD in diabetic patients at a lower cutoff value with inadequate sensitivity and specificity (cutoff value: -17.15%; sensitivity: 61.1%, specificity: 52.9%). In addition, the results for segmental PSLS were similar to those for global PSLS. In conclusion, global and segmental PSLSs at rest were significantly lower in patients with both obstructive CAD and diabetes mellitus than in patients with obstructive CAD only; thus, PSLSs at rest might not be a useful parameter in the detection of obstructive CAD in patients with diabetes mellitus.

CD151 promotes proliferation and migration of PC3 cells via the formation of CD151-integrin α3/α6 complex.

SummaryOver-expression of CD151 was found to be associated with metastasis and poor prognosis of prostatic carcinoma. This study was designed to examine the mechanism by which CD151 promotes the proliferation and migration of prostatic cancer cells. The pAAV-CD151, pAAV-GFP and pAAV-CD151-AAA mutant plasmids were constructed and used to transiently transfect PC3 cells (a prostatic carcinoma 3 cell line) by the mediation of Fugene HD. Then, the cells were assigned to control group, pAAV-GFP group, pAAV-CD151 group, and pAAV-CD151-AAA group respectively. Cell proliferation was evaluated by using the 3-[4,5-dimet-hylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method. Cell migration assay was performed by using Boyden chambers. The formation of CD151-integrin α3/α6 complex was determined by the method of co-immunoprecipitation. The protein expression levels of CD151 and extracellular signal-regulated kinase (ERK) were measured by Western blotting. The results showed that transfection of pAAV-CD151 or pAAV-CD151-AAA mutant increased the expression of CD151 protein in PC3 cells. Co-immunoprecipitation showed that more CD151-integrin α3/α6 complex was formed in the pAAV-CD151 group than in the control group, the pAAV-GFP group and the pAAV-CD151-AAA mutant group. Furthermore, the proliferative and migrating capacity of PC3 cells was substantially increased in the pAAV-CD151 group but inhibited in the pAAV-CD151-AAA mutant group. CD151 transfection increased the expression of phospho-ERK. Taken together, it was concluded that CD151 promotes the proliferation and migration of PC3 cells through the formation of CD151-integrin complex and the activation of phosphorylated ERK.Over-expression of CD151 was found to be associated with metastasis and poor prognosis of prostatic carcinoma. This study was designed to examine the mechanism by which CD151 promotes the proliferation and migration of prostatic cancer cells. The pAAV-CD151, pAAV-GFP and pAAV-CD151-AAA mutant plasmids were constructed and used to transiently transfect PC3 cells (a prostatic carcinoma 3 cell line) by the mediation of Fugene HD. Then, the cells were assigned to control group, pAAV-GFP group, pAAV-CD151 group, and pAAV-CD151-AAA group respectively. Cell proliferation was evaluated by using the 3-[4,5-dimet-hylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method. Cell migration assay was performed by using Boyden chambers. The formation of CD151-integrin α3/α6 complex was determined by the method of co-immunoprecipitation. The protein expression levels of CD151 and extracellular signal-regulated kinase (ERK) were measured by Western blotting. The results showed that transfection of pAAV-CD151 or pAAV-CD151-AAA mutant increased the expression of CD151 protein in PC3 cells. Co-immunoprecipitation showed that more CD151-integrin α3/α6 complex was formed in the pAAV-CD151 group than in the control group, the pAAV-GFP group and the pAAV-CD151-AAA mutant group. Furthermore, the proliferative and migrating capacity of PC3 cells was substantially increased in the pAAV-CD151 group but inhibited in the pAAV-CD151-AAA mutant group. CD151 transfection increased the expression of phospho-ERK. Taken together, it was concluded that CD151 promotes the proliferation and migration of PC3 cells through the formation of CD151-integrin complex and the activation of phosphorylated ERK.