title: Doxycycline Protects Thymic Epithelial Cells from Mitomycin C-Mediated Apoptosis In Vitro via Trx2-NF-κB-Bcl-2/Bax Axis.
abstract: OBJECTIVE
  Age-associated and stress-induced involution of the thymus is accompanied by reduced numbers of thymic epithelial cells (TECs) and severe reduction in peripheral T cell repertoire specificities. These events seriously affect immune function, but the mechanisms involved are unclear. Our preliminary findings showed that doxycycline (Dox) could drive the proliferation of a TEC line (MTEC1 cells) partially via the MAPK signaling pathway. Dox can also up-regulate IL-6 and GM-CSF expression via the NF-κB and MAPK/ERK pathways. Herein, we investigate the effects and mechanisms used by Dox that protect against mitomycin C (MMC)-induced MTEC1 cell apoptosis.
  
  
  METHODS
  MTEC1 cells were treated with Dox, MMC, and Dox plus MMC for different amounts of time. The expression of Trx2, NF-κB, Bcl-2, and Bax proteins were then detected by western blotting.
  
  
  RESULTS
  Our findings show that Dox protects MTEC1 cells from MMC-induced apoptosis. Dox up-regulated the expression of Trx2 and promoted NF-κB phosphorylation. Meanwhile, Dox also increased the expression of Bcl-2, partially reduced the expression of Bax, and normalized the ratio of Bcl-2 to Bax.
  
  
  CONCLUSIONS
  Dox exerts an anti-apoptosis function via the NF-κB-Bcl-2/Bax and Trx2-ASK1/JNK pathways in vitro. Therefore, Dox may represent a drug that could be used to attenuate thymic senescence, rescue thymic function, and promote T cell reconstitution.
authors.affiliation: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhuo
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Zhang
authors.forename: Fengyi
authors.initials: F
authors.lastname: Du
authors.forename: Sheng
authors.initials: S
authors.lastname: Xia
authors.forename: Qixiang
authors.initials: Q
authors.lastname: Shao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004318:Doxycycline / Q000494:pharmacology*; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D016328:NF-kappa B; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016685:Mitomycin; D013879:Thioredoxins; D004318:Doxycycline