10 results on '"Chi Ling Fu"'
Search Results
2. IPSE, an abundant egg-secreted protein of the carcinogenic helminth Schistosoma haematobium, promotes proliferation of bladder cancer cells and angiogenesis
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Evaristus C. Mbanefo, Chinwike Terry Agbo, Yuanlong Zhao, Olivia K. Lamanna, Kim H. Thai, Shannon E. Karinshak, Mohammad Afzal Khan, Chi-Ling Fu, Justin I. Odegaard, Irina V. Saltikova, Michael J. Smout, Luke F. Pennington, Mark R. Nicolls, Theodore S. Jardetzky, Alex Loukas, Paul J. Brindley, Franco H. Falcone, and Michael H. Hsieh
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Schistosoma haematobium, the helminth causing urogenital schistosomiasis, is a known bladder carcinogen. Despite the causal link between S. haematobium and bladder cancer, the underlying mechanisms are poorly understood. S. haematobium oviposition in the bladder is associated with angiogenesis and urothelial hyperplasia. These changes may be pre-carcinogenic events in the bladder. We hypothesized that the Interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE), an S. haematobium egg-secreted “infiltrin” protein that enters host cell nuclei to alter cellular activity, is sufficient to induce angiogenesis and urothelial hyperplasia. Methods: Mouse bladders injected with S. haematobium eggs were analyzed via microscopy for angiogenesis and urothelial hyperplasia. Endothelial and urothelial cell lines were incubated with recombinant IPSE protein or an IPSE mutant protein that lacks the native nuclear localization sequence (NLS-) and proliferation measured using CFSE staining and real-time monitoring of cell growth. IPSE’s effects on urothelial cell cycle status was assayed through propidium iodide staining. Endothelial and urothelial cell uptake of fluorophore-labeled IPSE was measured. Findings: Injection of S. haematobium eggs into the bladder triggers angiogenesis, enhances leakiness of bladder blood vessels, and drives urothelial hyperplasia. Wild type IPSE, but not NLS-, increases proliferation of endothelial and urothelial cells and skews urothelial cells towards S phase. Finally, IPSE is internalized by both endothelial and urothelial cells. Interpretation: IPSE drives endothelial and urothelial proliferation, which may depend on internalization of the molecule. The urothelial effects of IPSE depend upon its NLS. Thus, IPSE is a candidate pro-carcinogenic molecule of S. haematobium. Summary Schistosoma haematobium acts as a bladder carcinogen through unclear mechanisms. The S. haematobium homolog of IPSE, a secreted schistosome egg immunomodulatory molecule, enhances angiogenesis and urothelial proliferation, hallmarks of pre-carcinogenesis, suggesting IPSE is a key pro-oncogenic molecule of S. haematobium.
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- 2020
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3. A new mouse model for female genital schistosomiasis.
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Monica L Richardson, Chi-Ling Fu, Luke F Pennington, Jared D Honeycutt, Justin I Odegaard, Yi-Ju Hsieh, Olfat Hammam, Simon L Conti, and Michael H Hsieh
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Over 112 million people worldwide are infected with Schistosoma haematobium, one of the most prevalent schistosome species affecting humans. Female genital schistosomiasis (FGS) occurs when S. haematobium eggs are deposited into the female reproductive tract by adult worms, which can lead to pelvic pain, vaginal bleeding, genital disfigurement and infertility. Recent evidence suggests co-infection with S. haematobium increases the risks of contracting sexually transmitted diseases such as HIV. The associated mechanisms remain unclear due to the lack of a tractable animal model. We sought to create a mouse model conducive to the study of immune modulation and genitourinary changes that occur with FGS.To model FGS in mice, we injected S. haematobium eggs into the posterior vaginal walls of 30 female BALB/c mice. A control group of 20 female BALB/c mice were injected with uninfected LVG hamster tissue extract. Histology, flow cytometry and serum cytokine levels were assessed at 2, 4, 6, and 8 weeks post egg injection. Voiding studies were performed at 1 week post egg injection.Vaginal wall injection with S. haematobium eggs resulted in synchronous vaginal granuloma development within 2 weeks post-egg injection that persisted for at least 6 additional weeks. Flow cytometric analysis of vaginal granulomata revealed infiltration by CD4+ T cells with variable expression of the HIV co-receptors CXCR4 and CCR5. Granulomata also contained CD11b+F4/80+ cells (macrophages and eosinophils) as well as CXCR4+MerTK+ macrophages. Strikingly, vaginal wall-injected mice featured significant urinary frequency despite the posterior vagina being anatomically distant from the bladder. This may represent a previously unrecognized overactive bladder response to deposition of schistosome eggs in the vagina.We have established a new mouse model that could potentially enable novel studies of genital schistosomiasis in females. Ongoing studies will further explore the mechanisms by which HIV target cells may be drawn into FGS-associated vaginal granulomata.
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- 2014
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4. Schistosoma haematobium Egg Isolation
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Chi-Ling Fu and Michael Hsieh
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Biology (General) ,QH301-705.5 - Abstract
Schistosoma haematobiumis the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. Since most of the pathology in schistosomasis is directly attributable to the host reaction to eggs and egg-associated antigens, their isolation and study are important experimental techniques. S. haematobium eggs can be collected from infected tissues for injection into other animals or preparation of crude egg extracts. This protocol describes a simple way to isolate eggs.Schistosomes are a biohazard. Workers should wear latex gloves at all times when handling schistosomal materials or any tissues from infected animals.
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- 2012
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5. Transcriptional profiling of the bladder in urogenital schistosomiasis reveals pathways of inflammatory fibrosis and urothelial compromise.
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Debalina Ray, Tyrrell A Nelson, Chi-Ling Fu, Shailja Patel, Diana N Gong, Justin I Odegaard, and Michael H Hsieh
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the urine. Despite the global impact of urogenital schistosomiasis, basic understanding of the associated pathologic mechanisms has been incomplete due to the lack of suitable animal models. We leveraged our recently developed mouse model of urogenital schistosomiasis to perform the first-ever profiling of the early molecular events that occur in the bladder in response to the introduction of S. haematobium eggs. Microarray analysis of bladders revealed rapid, differential transcription of large numbers of genes, peaking three weeks post-egg administration. Many differentially transcribed genes were related to the canonical Type 2 anti-schistosomal immune response, as reflected by the development of egg-based bladder granulomata. Numerous collagen and metalloproteinase genes were differentially transcribed over time, revealing complex remodeling and fibrosis of the bladder that was confirmed by Masson's Trichrome staining. Multiple genes implicated in carcinogenesis pathways, including vascular endothelial growth factor-, oncogene-, and mammary tumor-related genes, were differentially transcribed in egg-injected bladders. Surprisingly, junctional adhesion molecule, claudin and uroplakin genes, key components for maintaining the urothelial barrier, were globally suppressed after bladder exposure to eggs. This occurred in the setting of urothelial hyperplasia and egg shedding in urine. Thus, S. haematobium egg expulsion is associated with intricate modulation of the urothelial barrier on the cellular and molecular level. Taken together, our findings have important implications for understanding host-parasite interactions and carcinogenesis in urogenital schistosomiasis, and may provide clues for novel therapeutic strategies.
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- 2012
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6. A novel mouse model of Schistosoma haematobium egg-induced immunopathology.
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Chi-Ling Fu, Justin I Odegaard, De'Broski R Herbert, and Michael H Hsieh
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, S. haematobium egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis.
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- 2012
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7. Macrophages are required for host survival in experimental urogenital schistosomiasis.
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Chi-Ling Fu, Odegaard, Justin I., and Hsieh, Michael H.
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GENITOURINARY diseases , *SCHISTOSOMIASIS , *SCHISTOSOMA haematobium , *FIBROSIS , *MACROPHAGES - Abstract
Urogenital schistosomiasis, Schistosoma haematobium worm infection, afflicts millions of people with egg-triggered, fibrotic bladder granulomata. Despite the significant global impact of urogenital schistosomiasis, the mechanisms of bladder granulomogenesis and fibrosis are ill defined due to the prior lack of tractable animal models. We combined a mouse model of urogenital schistosomiasis with macrophage-depleting liposomal clodronate (LC) to define how macrophages mediate bladder granulomogenesis and fibrosis. Mice were injected with eggs purified from infected hamsters or vehicle prepared from uninfected hamster tissues (xenoantigen and injection trauma control). Empty liposomes were controls for LC: 1) LC treatment resulted in fewer bladder egg granuloma-infiltrating macrophages, eosinophils, and T and B cells, lower bladder and serum levels of eotaxin, and higher bladder concentrations of IL-1α and chemokines (in a time-dependent fashion), confirming that macrophages orchestrate leukocyte infiltration of the egg-exposed bladder; 2) macrophage- depleted mice exhibited greater weight loss and bladder hemorrhage postegg injection; 3) early LC treatment postegg injection resulted in profound decreases in bladder fibrosis, suggesting differing roles for macrophages in fibrosis over time; and 4) LC treatment also led to egg dose-dependent mortality, indicating that macrophages prevent death from urogenital schistosomiasis. Thus, macrophages are a potential therapeutic target for preventing or treating the bladder sequelae of urogenital schistosomiasis. [ABSTRACT FROM AUTHOR]
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- 2015
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8. Transcriptional Profiling of the Bladder in Urogenital Schistosomiasis Reveals Pathways of Inflammatory Fibrosis and Urothelial Compromise.
- Author
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Ray, Debalina, Nelson, Tyrrell A., Chi-Ling Fu, Patel, Shailja, Gong, Diana N., Odegaard, Justin I., and Hsieh, Michael H.
- Abstract
Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the urine. Despite the global impact of urogenital schistosomiasis, basic understanding of the associated pathologic mechanisms has been incomplete due to the lack of suitable animal models. We leveraged our recently developed mouse model of urogenital schistosomiasis to perform the first-ever profiling of the early molecular events that occur in the bladder in response to the introduction of S. haematobium eggs. Microarray analysis of bladders revealed rapid, differential transcription of large numbers of genes, peaking three weeks post-egg administration. Many differentially transcribed genes were related to the canonical Type 2 anti-schistosomal immune response, as reflected by the development of egg-based bladder granulomata. Numerous collagen and metalloproteinase genes were differentially transcribed over time, revealing complex remodeling and fibrosis of the bladder that was confirmed by Masson's Trichrome staining. Multiple genes implicated in carcinogenesis pathways, including vascular endothelial growth factor-, oncogene-, and mammary tumorrelated genes, were differentially transcribed in egg-injected bladders. Surprisingly, junctional adhesion molecule, claudin and uroplakin genes, key components for maintaining the urothelial barrier, were globally suppressed after bladder exposure to eggs. This occurred in the setting of urothelial hyperplasia and egg shedding in urine. Thus, S. haematobium egg expulsion is associated with intricate modulation of the urothelial barrier on the cellular and molecular level. Taken together, our findings have important implications for understanding host-parasite interactions and carcinogenesis in urogenital schistosomiasis, and may provide clues for novel therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2012
- Full Text
- View/download PDF
9. Effects of overexpression of IL-10, IL-12, TGF-β and IL-4 on allergen induced change in bronchial responsiveness.
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Chi-Ling Fu, Yi-Ling Ye, Yueh-Lun Lee, and Bor-Luen Chiang
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ASTHMA , *ALLERGENS , *GENE expression , *AIRWAY (Anatomy) , *MICE as carriers of disease , *PLASMIDS , *INFLAMMATION , *DISEASES - Abstract
Background: An increasing prevalence of allergic diseases, such as atopic dermatitis, allergic rhinitis and bronchial asthma, has been noted worldwide. Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2) cells. This study aims to explore the therapeutic effect of the airway gene transfer of IL-12, IL-10 and TGF-β on airway inflammation in a mouse model of allergic asthma. Methods: BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA and challenged by nebulized OVA. Different cytokine gene plasmids or non-coding vector plasmids were instilled daily into the trachea up to one day before the inhalatory OVA challenge phase. Results: Intratracheal administration of IL-10, IL-12 or TGF-β can efficiently inhibit antigen-induced airway hyper-responsiveness and is able to largely significantly lower the number of eosinophils and neutrophils in bronchoalveolar lavage fluid of ovalbumin (OVA) sensitized and challenged mice during the effector phase. Furthermore, the effect of IL-10 plasmids is more remarkable than any other cytokine gene plasmid. On the other hand, local administration of IL-4 gene plasmids before antigen challenge can induce severe airway hyper-responsiveness (AHR) and airway eosinophilia. Conclusion: Our data demonstrated that anti- inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in murine model of asthma. [ABSTRACT FROM AUTHOR]
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- 2006
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10. Chapter Two - Macroscopic and microscopic imaging modalities for diagnosis and monitoring of urogenital schistosomiasis.
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Xie, Shelly, Shalaby-Rana, Eglal, Hester, Austin, Honeycutt, Jared, Chi-Ling Fu, Boyett, Deborah, Wen Jiang, and Hsieh, Michael H.
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MAGNETIC resonance imaging , *SCHISTOSOMIASIS , *DIAGNOSIS , *COMPUTED tomography - Abstract
Urogenital schistosomiasis remains a major global challenge. Optimal management of this infection depends upon imaging-based assessment of sequelae. Although established imaging modalities such as ultrasonography, plain radiography, magnetic resonance imaging (MRI), narrow band imaging, and computerized tomography (CT) have been used to determine tissue involvement by urogenital schistosomiasis, newer refinements in associated technologies may lead to improvements in patient care. Moreover, application of investigational imaging methods such as confocal laser endomicroscopy and two-photon microscopy in animal models of urogenital schistosomiasis are likely to contribute to our understanding of this infection's pathogenesis. This review discusses prior use of imaging in patients with urogenital schistosomiasis and experimentally infected animals, the advantages and limitations of these modalities, the latest radiologic developments relevant to this infection, and a proposed future diagnostic standard of care for management of afflicted patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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