Doxycycline enhances the Ras-MAPK signaling and proliferation of mouse thymic epithelial cells

✍ Scribed by Xun Chen; Sheng Xia; Rong Li; Hui Liu; Ying Huang; Xiaoping Qian; Xueyuan Xiao; Xun Xu; Xin Lin; Yuxiang Tian; Yangyong Zong; Dacheng He; Weifeng Chen; Yu Zhang; Qixiang Shao

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 372 KB
• Volume: 107
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22147

✦ Synopsis

Abstract

Depletion of T‐cell‐dependent immunity is a major consideration for patients suffering from infections of human immunodeficiency virus (HIV), those undergoing organ transplantation, and those receiving anti‐cancer chemotherapy and/or radiotherapy. In general, T‐cell regeneration occurs in the thymus through thymopoiesis. We have found that doxycycline (Dox), a tetracycline derivative, enhances the proliferation of mouse thymic epithelial cells, which are unique in their capacity to support positive selection and are essential throughout the development of thymocytes. Cell cycle analysis indicates that the increased cell proliferation is due to a shortened G~0~/G~1~ phase. To reveal the underlying mechanisms, we examined the expression of an array of molecules that regulate the cell cycle. The results show that in mouse thymic medullary‐type epithelial cell line 1 (MTEC1) Dox leads to elevated levels of H‐Ras, phosphorylated extracellular signal‐regulated kinase 1/2 (p‐ERK1/2), cyclin E, cyclin dependent kinase 4/2 (CDK4/CDK2), E2F3, and c‐myc. These data, and the observation that the proliferation‐enhancing effect is largely abolished following treatment with an ERK inhibitor support an active role of the Ras‐ERK/mitogen‐activated protein kinase (MAPK) signaling pathway. In conclusion, the present study reveals a new activity of an old family of antibiotics. The in vivo effect of Dox on immune reconstitution warrants further exploration. J. Cell. Biochem. 107: 494–503, 2009. © 2009 Wiley‐Liss, Inc.