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Original Article

IL-4 Independent Nuclear Translocalization of STAT6 in HeLa Cells by Entry of Toxoplasma gondii
Hye-Jin Ahn, Ji Yeon Kim, Ho-Woo Nam
Korean J Parasitol 2009;47(2):117-124.
Published online May 27, 2009
DOI: https://doi.org/10.3347/kjp.2009.47.2.117

Toxoplasma gondii provokes rapid and sustained nuclear translocation of the signal transducer and activator of transcription 6 (STAT6) in HeLa cells. We observed activation of STAT6 as early as 2 hr after infection with T. gondii by the nuclear translocation of fluorescence expressed from exogenously transfected pDsRed2-STAT6 plasmid and by the detection of phosphotyrosine-STAT6 in Western blot. STAT6 activation occurred only by infection with live tachyzoites but not by co-culture with killed tachyzoites or soluble T. gondii extracts. STAT6 phosphorylation was inhibited by small interfering RNA of STAT6 (siSTAT6). In view of the fact that STAT6 is a central mediator of IL-4 induced gene expression, activation of STAT6 by T. gondii infection resembles that infected host cells has been stimulated by IL-4 treatment. STAT1 was affected to increase the transcription and expression by the treatment of siSTAT6. STAT6 activation was not affected by any excess SOCS's whereas that with IL-4 was inhibited by SOCS-1 and SOCS-3. T. gondii infection induced Eotaxin-3 gene expression which was reduced by IFN-γ. These results demonstrate that T. gondii exploits host STAT6 to take away various harmful reactions by IFN-γ. This shows, for the first time, IL-4-like action by T. gondii infection modulates microbicidal action by IFN-γ in infected cells.

Citations

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  • Nuclear Localization and Cleavage of STAT6 Is Induced by Kaposi’s Sarcoma-Associated Herpesvirus for Viral Latency
    Chong Wang, Caixia Zhu, Fang Wei, Shujun Gao, Liming Zhang, Yuhong Li, Yanling Feng, Yin Tong, Jianqing Xu, Bin Wang, Zhenghong Yuan, Erle S. Robertson, Qiliang Cai, Paul D. Ling
    PLOS Pathogens.2017; 13(1): e1006124.     CrossRef
  • SAG5B and SAG5C combined vaccine protects mice against Toxoplasma gondii infection
    Gang Lu, Jian Zhou, Aihua Zhou, Yali Han, Jingjing Guo, Pengxia Song, Huaiyu Zhou, Hua Cong, Ming Hou, Lin Wang, Shenyi He
    Parasitology International.2017; 66(5): 596.     CrossRef
  • SAG4 DNA and Peptide Vaccination Provides Partial Protection against T. gondii Infection in BALB/c Mice
    Jian Zhou, Lin Wang
    Frontiers in Microbiology.2017;[Epub]     CrossRef
  • Afatinib Reduces STAT6 Signaling of Host ARPE-19 Cells Infected with Toxoplasma gondii
    Zhaoshou Yang, Hye-Jin Ahn, Young-Hoon Park, Ho-Woo Nam
    The Korean Journal of Parasitology.2016; 54(1): 31.     CrossRef
  • Chronic Toxoplasmosis Modulates the Induction of Contact Hypersensitivity by TNCB in Mouse Model
    Zhaoshou Yang, Hye-Jin Ahn, Ho-Woo Nam
    The Korean Journal of Parasitology.2015; 53(6): 755.     CrossRef
  • Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity
    Huihui Chen, Hui Sun, Fuping You, Wenxiang Sun, Xiang Zhou, Lu Chen, Jing Yang, Yutao Wang, Hong Tang, Yukun Guan, Weiwei Xia, Jun Gu, Hiroki Ishikawa, Delia Gutman, Glen Barber, Zhihai Qin, Zhengfan Jiang
    Cell.2011; 147(2): 436.     CrossRef
  • Deactivation of STAT6 through Serine 707 Phosphorylation by JNK
    Takashi Shirakawa, Yoshinori Kawazoe, Tomoko Tsujikawa, Dongju Jung, Shin-ichi Sato, Motonari Uesugi
    Journal of Biological Chemistry.2011; 286(5): 4003.     CrossRef
  • Coactivator P100 Protein Enhances STAT6‐Dependent Transcriptional Activation But Has No Effect on STAT1‐Mediated Gene Transcription
    Xinting Wang, Xin Liu, Jianfei Fang, Yanxin Lu, Jinyan He, Xuyang Yao, Zhi Yao, Jie Yang
    The Anatomical Record.2010; 293(6): 1010.     CrossRef
  • Toxoplasma Rhoptry Protein 16 (ROP16) Subverts Host Function by Direct Tyrosine Phosphorylation of STAT6
    Yi-Ching Ong, Michael L. Reese, John C. Boothroyd
    Journal of Biological Chemistry.2010; 285(37): 28731.     CrossRef
  • STAT6 activation by Toxoplasma gondii infection induces the expression of Th2 C-C chemokine ligands and B clade serine protease inhibitors in macrophage
    Hye-Jin Ahn, Ji Yeon Kim, Kyung-Ju Ryu, Ho-Woo Nam
    Parasitology Research.2009; 105(5): 1445.     CrossRef
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Mini Review

Clinical and Pathological Aspects of Filarial Lymphedema and Its Management
R. K. Shenoy
Korean J Parasitol 2008;46(3):119-125.
Published online September 20, 2008
DOI: https://doi.org/10.3347/kjp.2008.46.3.119

Lymphatic filariasis, transmitted by mosquitoes is the commonest cause of lymphedema in endemic countries. Among 120 million infected people in 83 countries, up to 16 million have lymphedema. Microfilariae ingested by mosquitoes grow into infective larvae. These larvae entering humans after infected mosquito bites grow in the lymphatics to adult worms that cause damage to lymphatics resulting in dilatation of lymph vessels. This earliest pathology is demonstrated in adults as well as in children, by ultrasonography, lymphoscintigraphy and histopathology studies. Once established, this damage was thought to be irreversible. This lymphatic damage predisposes to bacterial infection that causes recurrent acute attacks of dermato-lymphangio-adenitis in the affected limbs. Bacteria, mainly streptococci gain entry into the lymphatics through 'entry lesions' in skin, like interdigital fungal infections, injuries, eczema or similar causes that disrupt integrity of skin. Attacks of dermato-lymphangio-adenitis aggravates lymphatic damage causing lymphedema, which gets worse with repeated acute attacks. Elephantiasis is a late manifestation of lymphatic filariasis, which apart from limbs may involve genitalia or breasts. Lymphedema management includes use of antifilarial drugs in early stages, treatment and prevention of acute attacks through 'limb-hygiene', antibiotics and antifungals where indicated, and physical measures to reduce the swelling. In selected cases surgery is helpful.

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Original Article

Excretory/secretory proteins (ESP) from Toxoplasma gondii were analyzed to define the function in the penetration process into host cells. Whole ESP obtained at 37℃ were composed of 15 bands with molecular mass of 110, 97, 86, 80, 70, 60, 54, 42, 40, 36, 30, 28, 26, 22, and 19 kDa. Five ESP of 86, 80, 42, 36, and 28 kDa were reacted with monoclonal antibodies (mAb), named as Tg386 (microneme), Tg485 (surface membrane), Tg786 (rhoptry), Tg378, and Tg556 (both dense granules), respectively. The ESP was released by a temperature-dependent/-independent manner and all at once whenever ready to pour out except Tg786. Each ESP was not exhausted within the parasite but the amount was limited. Tg786 was released continuously with increment, whereas Tg378 and Tg556 were ceased to release after 3 and 4 hr. Dense granular Tg378 and Tg556 were released spontaneously and constitutively before the entry into host cells also. The entry of T. gondii was inhibited by all the mAbs differentially. And the parasite deprived of ESP was inhibited to enter exponentially up to 90.1%. It is suggested that ESP play an essential function to provide appropriate environment for the entry of the parasite into host cells.

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