title: Survival of porcine fibroblasts enhanced by human FasL and dexamethasone-treated human dendritic cells in vitro.
abstract: Cell-mediated and acute vascular rejections remain to be one of the primary hurdles to achieve successful xenotransplantation. Fas ligand is known to be an important molecule for the formation of 'immune-privileged' condition and dendritic cells treated with dexamethasone (Dex-DCs) acting like tolerogenic DCs (tDCs) which are known to protect transplanted cells and organs from unwanted immune responses. The present study investigated the possibility that porcine fibroblasts expressing human Fas ligand (PhF) together with human Dex-DCs could induce prolonged survival of porcine fibroblasts in vitro. PhF was collected from an ear of human Fas ligand transgenic porcine and cell-line was established by MGEM Inc. PhF labeled with CFSE co-cultured with human peripheral blood mononuclear cells (hPBMCs) were examined with respect to induction of tolerance and cell death when co-cultured with Dex-DCs for 3days. PhF induced the apoptosis in hPBMCs, especially CD4(+) T cells. Dex-DCs showed significant (P<0.05) reduction on the expression of CD80, CD86 and MHC class I/II, and the secretion of IL-12p70, TNF-α and IL-10, but increase of latency-associated peptide (LAP). Survival of PhF was significantly higher than that of WT and it was increased in the presence of Dex-DCs when compared to the other DCs (i.e.,DCs, LPS-treated DCs and LPS/Dex-treated DCs) in vitro. Survival of PhF did not change by co-culture with Dex-DCs due to apoptotic cell death of Dex-DCs. Dex-DCs reduced the death of porcine fibroblasts and, at the same time, PhF induced the apoptosis from hPBMCs, but it was not synergistic.
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors: In Kyu
authors: IK
authors: Lee
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Young Min
authors: YM
authors: Son
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Young Jun
authors: YJ
authors: Ju
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Sun Kwang
authors: SK
authors: Song
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; WCU Biomodulation major and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors: Minjung
authors: M
authors: Gu
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; WCU Biomodulation major and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors: Ki-Duk
authors: KD
authors: Song
authors: Animal Biotechnology Division, National Institute of Animal Science, RDA, Suwon, Republic of Korea.
authors: Hwi-Cheul
authors: HC
authors: Lee
authors: Animal Biotechnology Division, National Institute of Animal Science, RDA, Suwon, Republic of Korea.
authors: Jae-Seok
authors: JS
authors: Woo
authors: MGEN, Inc., Seoul, Republic of Korea.
authors: Jae Goo
authors: JG
authors: Seol
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; WCU Biomodulation major and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors: Sung Moo
authors: SM
authors: Park
authors: Department of Oral Microbiology & Immunology, DRI, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors: Seung Hyun
authors: SH
authors: Han
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; WCU Biomodulation major and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea. Electronic address: cyun@snu.ac.kr.
authors: Cheol-Heui
authors: CH
authors: Yun
mesh_terms: D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D053222:Fas Ligand Protein / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008297:Male; D013552:Swine
chemical_list: D000893:Anti-Inflammatory Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D003907:Dexamethasone
keywords: Apoptosis; Dendritic cell; Dexamethasone; FasL; Tolerance; Xenotransplantation