Vimentin is involved in peptidylarginine deiminase 2-induced apoptosis of activated Jurkat cells.
Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a Ca2+-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease. To investigate the role of PADI2 in apoptosis, we generated a Jurkat cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter, and used a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin to activate Jurkat cells. We found that PADI2 overexpression reduced the cell viability of activated Jurkat cells in1a dose- and time-dependent manner. The PADI2-overexpressed and -activated Jurkat cells presented typical manifestations of apoptosis, and exhibited greater levels of citrullinated proteins, including citrullinated vimentin. Vimentin overexpression rescued a portion of the cells from apoptosis. In conclusion, PADI2 overexpression induces apoptosis in activated Jurkat cells. Vimentin is involved in PADI2-induced apoptosis. Moreover, PADI2-overexpressed Jurkat cells secreted greater levels of vimentin after activation, and expressed more vimentin on their cell surfaces when undergoing apoptosis. Through artificially highlighting PADI2 and vimentin, we demonstrated that PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. The secretion and surface expression of vimentin are possible ways of autoantigen presentation to the immune system.
Department of Medicine, Da-Chien General Hospital, Taiwan, Republic of China.
Pei-Chen
PC
Hsu
Department of Applied Chemistry, Chaoyang University of Technology, Taiwan, Republic of China.
Ya-Fan
YF
Liao
Institute of Medicine, Chung Shan Medical University.
Chin-Li
CL
Lin
Wen-Hao
WH
Lin
Institute of Microbiology and Immunology, Chung Shan Medical University, and Division of Allergy, Immunology, and Rheumatology, Chung Shan Medical University Hospital, Taiwan, Republic of China.
Guang-Yaw
GY
Liu
Hui-Chih
HC
Hung
D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases; D014746:Vimentin / Q000502:physiology*
D014746:Vimentin; D002956:Citrulline; D006867:Hydrolases; C000620352:PADI2 protein, human; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases