Hui Jun Liu

Role of CREB in vasoactive intestinal peptide-mediated wound healing in human bronchial epithelial cells

Vasoactive intestinal peptide (VIP) is one of the most important sensory neuropeptides in respiratory system. We previously reported that VIP enhances wound healing and proliferation of human bronchial epithelial cells (HBECs), and these effects are mediated by intracellular signaling molecules such as protein kinase A (PKA), protein kinase C (PKC), Calmodulin (CaM), and extracellular signal-regulated kinase (ERK). In the present study, we further investigated the role of cAMP Response Element Binding Protein (CREB) in VIP-promoted protective effects in mechanical-damaged HBECs. VIP-mediated wound healing and cell proliferation in HBECs was inhibited by CREB antisense oligonucleotides (ASO) in a time-dependent manner. VIP increased the CREB DNA binding activity and expression of the p-CREB that were inhibited by VIP receptor antagonist. Increased CREB DNA binding activity and expression of the p-CREB were also partially inhibited by PKA and ERK inhibitors. These results suggest that the VIP-mediated wound repair of HBECs is associated with activation of CREB via PKA and ERK dependent pathway.

Cloning of a novel protein interacting with BRS-3 and its effects in wound repair of bronchial epithelial cells.

Bombesin receptor subtype 3 (BRS-3), the orphan bombesin receptor, may play a role in the regulation of stress responses in lung and airway epithelia. Bombesin receptor activated protein (BRAP )is a novel protein we found in our previous study which interacts with BRS-3. This study was designed to observe the subcellular location and wound repair function of BRAP in human bronchial epithelial cells (HBECs). BRAP ORF was amplified by RT-PCR and ligated to pEGFP-C1 vector, and then the recombinant plasmid pEGFP-C1-BRAP was transfected into Hela cells. The location of BRAP protein was observed by laser confocal microscope, and the expression of it was analyzed by Western-blot. At the same time,we built the recombinant plasmid pcDNA3.1(+)-BRAP, transfected it into HBECs and observed its impact on cell cycle and wound repair of HBECs. The results showed that BRAP locates in membrane and cytoplasm and increases significantly in transfected cells. Flow cytometry results demonstrated that the recombinant plasmid increases S phase plus G2 phase of cell cycle by 25%. Microscopic video analysis system showed that the repair index of wounded HBECs increases by 20% through stable expression of BRAP. The present study demonstrated that BRAP locates in the membrane and cytoplasm, suggesting that this protein is a cytoplasm protein, which promotes cell cycle and wound repair of HBECs.

Adipokine adiponectin is a potential protector to human bronchial epithelial cell for regulating proliferation, wound repair and apoptosis: Comparison with leptin and resistin

Epidemiological data indicate an increasing incidence of asthma in the obese individuals recent decades, while very little is known about the possible association between them. Here, we compared the roles of adipocyte-derived factors, including leptin, adiponectin and resistin on proliferation, wound repair and apoptosis in human bronchial epithelial cells (HBECs) which play an important role in the pathogenesis of asthma. The results showed that exogenous globular adiponectin (gAd) promoted proliferation, cell-cycle and wound repair of HBECs. This effect may be relevant to Ca(2+)/calmodulin signal pathway. Besides, gAd inhibited apoptosis induced by ozone and release of lactate dehydrogenase (LDH) of HBECs via regulated adipoR1 and reactive oxygen species. No effects of leptin or resistin on proliferation, wound repair and apoptosis of HBECs were detectable. These data indicate that airway epithelium is the direct target of gAd which plays an important role in protecting HBECs from mechanical or oxidant injuries and may have therapeutic implications in the treatment of asthma.

Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials

The single‐tablet regimen rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) for treatment of HIV‐1‐infected adults was approved based on bioequivalence. We assessed the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF.

Effect of calcitonin gene-related peptide on E-cadherin expression in human bronchial epithelial cells

proliferation after treated with lactoferrin (10 mmol/L) for 24 hours and 48 hours respectively, and the results of western blot showed that LTF inhibited proliferation of nasopharyngeal carcinoma cells in vitro by modulating the mitogen-activated protein kinase pathway. This work was supported by National Key Project of Scientific Research Program (NO.2006CB910502, NO.2006CB910504); National Natural Sciences Foundation of China, Grant numbers: 30700469; the Special Funds of Science & Technology Departments of Hunan Province, China (05SK1001_1); the national innovative experimental plan for undergraduate (YA07050).

Down‐regulation of integrin beta‐4 on human bronchial epithelial cells leads to inhibition of proliferation, wound repair and restricted anti oxidative damage

labeled proteins isolated from the normal human sperm and separated on the same 2-D gel along with a Cy2-labeled mixture of all samples as an internal standard. For the other gel, we labeled the sample reversed. Over 61 protein spots were analyzed in each paired normal/abnormal comparison, and using DIGE technology with the mixed-sample internal standard, 36 protein spots were identified by ms/ms as showing significant changes (paired t-test, p<0.05) in the level of expression between normal and round-headed. 9 proteins were up-regulated and 27 proteins were down-regulated in round-headed. These proteins seem to play important roles in a variety of pathways including spermatogenesis, cell signaling, cell skeleton and metabolism.

Effect of antiflammin-1 on cytokines release from lipopolysaccharide-stimulated rat alveolar macrophages

day to 300 days. Compared with uninfected control, the level of all cytokines was significantly increased in infection. The level of IL-2 and TNF-a reached peak at 120 days post infection and sharply went down on 200day post infection. Highest level of IFN-r was detected after 160 day and decreased slowly after 240 days post infection. The levels of IL-4, IL-5, IL-10 were lower before 120 days and increased quickly after 160day and reached peak at 240 days post infection. These results suggest that mice immune types were affected by infection of Echinococcus granulosus (E.g) and elicited both Th1 and Th2 cell activation: Th1 played an important role at early stage of infection and Th2 played an important role in late stage of infection. The Th1 response benefited the host, whereas the Th2 response benefited the parasite. Thus Th1/Th2 polarization played an important role in the development of echinococcosis. To study the mechanism of immune protection against challenge infection with E.g protoscoleces in mice induced with Eg95 genetic vaccine, the mice were immunized 4 times with Eg95 genetic vaccine and then infected with protoscoleces. Compared to the infected group, the results showed the levels of Th1 cytokines (IL-2, IFN-r, TNF-a) were significantly enhanced and the levels of Th2 cytokines (IL-4, IL-5, IL-10) were slightly declined after vaccination with Eg95 genetic vaccine at 200day post infection. The results indicated that the balance of Th1/Th2 cytokines in murine sera infected with protoscoloces could be modulated by Eg95 genetic vaccine. Thus we deduced that protection against echinococcosis induced with Eg95 genetic vaccine was associated with predominate Th1-like responses.