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Journal : Indonesian Journal of Cancer Chemoprevention

Cyclosporine A and FK506 as Potent Inhibitors of Streptococcus intermedius Intermedilysin-Induced NFAT-1 Activation Susilowati, Heni; Okamura, Hirohiko; Hirota, Katsuhiko; Yoshida, Kaya; Tabata, Atsushi; Nagamune, Hideaki; Haneji, Tatsuji; Miyake, Yoichiro
Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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Abstract

Cyclosporine A (CsA) and tacrolimus (FK506), a member of calcineurin inhibitors, inhibit inflammation process as part of immune response. Nuclear activated T cells subfamily NFAT1 is a trascription factor responsible for the regulation of immune response genes. Streptococcus intermedius, an oral commensal bacterium, has been shown to strongly associate with liver abscess.  The S. intermedius strains produce intermedilysin (ILY), which is responsible for the bacterial virulence. Cyclosporine A and FK506 have been widely used to control NFAT activation in most of cell types, however the ability of CsA and FK506 to inhibit ILY-induced NFAT1 activation remains to be investigated. The aim of this study was to investigate the effect of  CsA and FK506 on NFAT1 activation caused by ILY. Human cholangiocellular cell line HuCCT1 was stimulated with various concentrations of ILY. The cell and nuclear morphological change was observed by microscopy analysis. The NFAT1 nuclear translocation that indicates its activation was detected by immunocytochemistry. The inhibitory effect of CsA and FK506 was tested after 30 min application before ILY treatment by using immunofluorescence microscope. The results showed cell and nuclear shrinkage in ILY-treated cells. The NFAT1 was translocated to the nuclei in HuCCT1 cells, and observed in dose dependent manner.  Cyclosporine A and FK506 inhibited ILY-induced NFAT1 nuclear translocation.  In conclusion, CsA and FK506 may act as potent inflammation control agents in S. intermedius ILY-infected cells.
Co-Authors Ady, Pangeran Pandu Bayu Agustinus Rudolf Phym, Agustinus Agustiya, Arvi Alma Linggar Jonarta Andriana, Myra Anne Handrini Dewi Aprilia, Sintya Asikin Nur Atsushi Tabata Ayun Febriana Azzahra, Annisa Annur Dea Cahyani, Yessica Denise Utami Putri, Denise Utami Devi Chretella Maheswara, Devi Chretella Dewi Agustina Dewi Widyaningsih Dewi Widyaningsih Dyah Irnawati Dyah Listyarifah Edy Meiyanto Endah Kusumastuti Fahlevi, Bunga Farida, Dwi Ana Farmasyanti, Cendrawasih Andusyana Fery Setiawan Hanif, Hilmy Irsyadi Hardiyani, Reisca Tiara Hargyatni, Titin Hary Hermawan Hayuningtyas, Widya Galuh Henny Henny, Henny Heribertus Dedy Kusuma Yulianto Hermawan Prasetyanto HIDAYAT, ERWAN NUR Hideaki Nagamune Hirohiko Okamura Innayati Oktiana Yudasari, Innayati Oktiana Intan Ruspita, Intan Irsalina, Nadia Iswari, Febri Nandia Sri Jaelani, Jaelani Juni Handajani Katsuhiko Hirota Kaya Yoshida Kuijpers-Jagtman, Anne Marie Kustami, Endang Kusumaningsih, Dhevi Dadi Kusumaningtyas, Dhevi Dadi Lisdrianto Hanindriyo Lukis, Prima Agusti Mariana, Septanus Rita Maulana, Putri Anindya Mohammad Khafid Mu'tashim, Muhammad Faris Mun‘im, Abdul Nunuk Purwanti Pertiwi, Heppy Atma Prabowo, Adi Prakosa, Basma Rosandi Prawira, Anggun Wida Ratnaningrum Ratnaningrum, Ratnaningrum Retnosari Andrajati Sati, Dian Laras Selvy, Mutiara Septiani, Intan Dzahabiyah Shofiana, Umu Salma Siagian, JW Siti Sunarintyas Siwi, Dyanasti P. Sulistyowati, Pemilia Suryani Hutomo, Suryani Suryanto, Yanti Ivana Tatsuji Haneji Titin Hargyatni Trianna Wahyu Utami Wijayanti, Afifah Arum Wulandari Wulandari Yoga, Ika Yoichiro Miyake Yosaphat Bayu Rosanto Ziadah, Tsai'un Nur