Browsing by Author "Hsu, Wei-Tung"

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A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis
(2010-02-05)
Lin, Chen-Si
;
He, Pei-Juin
;
Tsai, Nu-Man
;
Li, Chi-Han
;
Yang, Shang-Chih
Helicobacter pylon has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This Study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell Proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis. (C) 2010 Elsevier Inc. All rights reserved.
A RAPID AND CONVENIENT METHOD TO ENHANCE TRANSGENIC EXPRESSION IN TARGET CELLS
(2012)
Chen, Chia-Hung
;
Liu, Yen-Ku
;
Lin, Yu-Ling
;
Chuang, Huai-Yao
;
Hsu, Wei-Tung
Gene therapy provides a novel strategy and a new hope for patients with cancer. Unfortunately, the specifics of the delivery systems or the promoters have not achieved the specified efficacy so far, and the perfection of either system will be extremely difficult. In this study, we introduce a simple concept that a combination of a partially specific delivery system and a partially specific promoter activity may achieve a more specific effect on transgenic expression in target cells. The first section describes tumor-related transcription factors that were assayed in tumors or rapidly proliferating cells to determine their activities. The activities of nuclear factor (NF)-kappa B, CREB, and HIF-1 were higher, and three copies of each response element were used to construct a transcription factor-based synthetic promoter (TSP). The results showed that the expression of the TSP was active and partially specific to cell types. As described in the second section, the multifunctional peptide RGD-4-CHA was designed to absorb polyethyleneimine (PEI) molecules, and this complex was targeted to integrin alpha v beta 3 on B16F10 cells. The results indicated that RGD-4C-HA could associate with PEI to mediate specific targeting in vitro. Finally, the combination of the PEI-peptide complex and TSP could enhance the specifically transgenic expression in B16F10 cells. This strategy has been proven to work in vitro and might potentially be used for specific gene therapy in vivo.
A Soybean Oil-Based Liposome-Polymer Transfection Complex as a Codelivery Systemfor DNA and Subunit Vaccines
(2012)
Lin, Yu-Ling
;
Chen, Li-Yi
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Chen, Chia-Hung
;
Liu, Yen-Ku
;
Hsu, Wei-Tung
Inexpensive liposome-polymer transfection complexes (LPTCs) were developed and used as for DNA or protein delivery. The particle sizes of the LPTCs were in the range of 212.2 to 312.1 nm, and the zetapotential was +38.7 mV. LPTCs condensed DNA and protected DNA from DNase I digestion and efficiently delivered LPTC/DNA complexes in Balb/3T3 cells. LPTCs also enhanced the cellular uptake of antigen in mouse macrophage cells and stimulated TNF-alpha release in naive mice splenocytes, both indicating the potential of LPTCs as adjuvants for vaccines. In vivo studies were performed using H. pylori relative heat shock protein 60 as an antigen model. The vaccination of BALB/c mice with LPTC-complexed DNA and protein enhanced the humoral immune response. Therefore, we developed a DNA and protein delivery system using LPTCs that is inexpensive, and we successfully applied it to the development of a DNA and subunit vaccine.
Antibodies against Helicobacter pylori heat shock protein 60 aggravate HSP60-mediated proinflammatory responses
(2011-08-01)
Liao, Kuang-Wen
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Lin, Chen-Si
;
Chen, Wen-Liang
;
Yang, Chu-Ting
;
Lin, Ching-Min
Anti-Helicobacter pylori heat shock protein 60 (HpHSP60) antibodies are Usually found in H. pylori-infected patients and are known to be associated with the progression of gastric diseases. However, the effects of these antibodies on the functions of HpHSP60 have not been identified. This study aims to investigate the effects of the interaction between anti-HSP60 antibodies and HpHSP60 on inflammatory responses. Anti-HpHSP60 polyclonal sera and monoclonal antibodies (mAbs) were produced to evaluate their effects on HpHSP60-induced IL-8 and TNF-alpha activity. The results indicated that anti-HpHSP60 polyclonal sera collected from patients infected with H. pylori or from rabbit and mice immunized with HpHSP60 could significantly enhance HpHSP60-mediated IL-8 and TNF-alpha secretion from monocytic THP-1 cells. Similar effects were also found with anti-HpHSP60 mAbs. Further analysis revealed that this phenomenon was only carried out by anti-HpHSP60 antibody but not by other non-specific mAbs. Moreover, the non-specific mAbs decreased the synergism of HpHSP60 and anti-HpHSP60 mAbs in proinflammatory cytokine induction. Herein, we have examined the role of anti-HpHSP60 antibody in host immune responses for the first time. This study demonstrated that H. pylori HSP60/mAbs could modulate helico-bacterial pathogenesis by increasing IL-8 and TNF-alpha production. The pathogen-specific antibodies may execute potential immune functions rather than recognize or neutralize microbes. (C) 2011 Elsevier Ltd. All rights reserved.
Characterizing the polymeric status of Helicobacter pylori heat shock protein 60
(2009-10-16)
Lin, Ching-Yi
;
Huang, Yu-Shan
;
Li, Chi-Han
;
Hsieh, Yuan-Ting
;
Tsai, Nu-Man
Helicobacter pylori heat shock protein 60 (HpHsp60) was first identified as an adhesion molecule associated with H. pylori infection. Here we have analyzed the structure of HpHsp60 via amino acid BLAST, circular dichroism, and electrophoresis and the results indicate that most recombinant HpHsp60 molecules exist as dimers or tetramers, which is quite different from Escherichia coli Hsp60. Treatment of human monocytic cells THP-1 with HpHsp60 was found to up-regulate a panel of cytokines including IL-1 alpha, IL-8, IL-10, IFN-gamma, TNF-alpha, TGF-beta, GRO, and RANTES. Carboxymethylated HpHsp60 molecules with a switched oligomeric status were able to further enhance NF-kappa B-mediated IL-8 and TNF-alpha secretion in THP-1 cells compared to unmodified HpHsp60 molecules. These results indicated that the oligomeric status of HpHsp60s might have an important role in regulating host inflammation and thus help facilitate H. pylori persistent infection. (C) 2009 Elsevier Inc. All rights reserved.
Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway
(2010-06-25)
Lin, Chen-Si
;
He, Pei-Juin
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Hsu, Wei-Tung
;
Wu, Ming-Shiang
;
Wu, Chang-Jer
Helicobacter pylori is a potent carcinogen associated with gastric cancer malignancy. Recently. H. pylori Heat shock protein 60 (HpHSP60) has been reported to promote cancer development by inducing chronic inflammation and promoting tumor cell migration. This study demonstrates a role for HpHSP60 in angiogenesis, a necessary precursor to tumor growth. We showed that HpHSP60 enhanced cell migration and tube formation, but not cell proliferation, in human umbilical vein endothelial cells (HUVECs). HpHSP60 also indirectly promoted HUVEC proliferation when HUVECs were co-cultured with supernatants collected from HpHSP60-treated AGS or THP-1 cells. The angiogenic array showed that HpHSP60 dramatically induced THP-1 cells and HUVECs to produce the chemotactic factors IL-8 and GRO. Inhibition of CXCR2, the receptor for IL-8 and GRO, or downstream PLC beta 2/Ca2+-mediated signaling, significantly abolished HpHSP60-induced tube formation. In contrast, suppression of MAP K or PI3 K signaling did not affect HpHSP60-mediated tubulogenesis. These data suggest that HpHSP60 enhances angiogenesis via CXCR2/PLC beta 2/Ca2+ signal transduction in endothelial cells. (C) 2010 Elsevier Inc. All rights reserved.
Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T cells
(2013-05-01)
Hsu, Wei-Tung
;
Wu, Ming-Shiang
;
Wu, Chang-Jer
;
Chen, Chia-Hung
;
Jian, Ting-Yan
Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T-cells associated with persistent infection
(2018-06-01)
Hsu, Wei-Tung
;
Ho, Shu-Yi
;
Jian, Ting-Yan
;
Huang, Han-Ning
;
Lin, Yu-Ling
Local Treg responses are involved in Helicobacter pylori-related inflammation and clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an important virulence factor associated with gastric carcinogenesis. This study to investigate the role of HpHSP60 in immunosuppression, particularly with regard to whether it could induce the production of Treg cells. For this purpose, human peripheral blood mononuclear cells (PBMCs) were treated with or without HpHSP60 in the presence of an anti-CD3 mAb to determine the effect of HpHSP60 on cell proliferation. In this report, HpHSP60 decreased the expression of CDK4 to significantly arrest the proliferation of mitogen-stimulated T-cells, which correlated with the induction of Treg cells. Moreover, monocytic cells were essential for the induction of HpHSP60-induced Treg cells via the secretion of IL-10 and TGF-beta after treatment with HpHSP60. Blockage of HpHSP60 with specific monoclonal antibodies significantly reduced the colonization of H. pylori and the expression of Treg cells in vivo. Overall, our results suggest that HpHSP60 could act on macrophages to trigger the expression of IL-10 and TGF-beta, thereby leading to an increase in Treg cells and inhibition of T-cell proliferation.