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ORIGINAL RESEARCH ARTICLE

Beneficial Effects of Treatment with Transglutaminase Inhibitor Cystamine on Macrophage Response in NZB/W F₁ Mice

Tsai-Ching Hsu^*, Szu-Yi Chiang, Chih-Yang Huang, Gregory J. Tsay^*,, Chiao-Wen Yang^*, Chien-Ning Huang and Bor-Show Tzang^||,1

^* Institute of Immunology, Chung Shan Medical University, Taichung 40203, Taiwan, R.O.C; Department of Health, Executive Yuan, Hua-Lien Hospital, Hua-Lien 97061, Taiwan, R.O.C; Graduate Institute of Chinese Medical Science, China Medical University, Taichung 40402, Taiwan, R.O.C; Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40203, Taiwan, R.O.C.; ^|| Institutes of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 40203, Taiwan, R.O.C.

To whom requests for reprints should be addressed at ¹ Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, R.O.C. 110 section 1, Chien Kuo N. Road, Taichung 402, Taiwan, R.O.C. E-mail: bstzang{at}csmu.edu.tw

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder of unknown etiology. However, the definitive mechanisms remain obscure. Recently, transglutaminase 2 (TG2) was implicated in the pathogenesis of SLE. Cystamine, which inactivates TG2 activity by forming a mixed disulfide, may interfere with and inhibit other thiol-dependent enzymes such as caspases. To investigate the effects of cystamine in SLE pathogenesis, this in vivo study assessed the serum and macrophage response after administration of cystamine to NZB/W F₁ mice. The experimental results demonstrated for the first time a significant reduction in TG2 and matrix metalloproteinase (MMP)-9 activity; tissue inhibitor of metalloproteinases (TIMP)-1, TIMP-2, TG2, tumor necrosis factor alpha, and tumor growth factor beta mRNA expression; and anticardiolipin autoantibodies (aCL) in NZB/W F₁ mice following cystamine administration. It strongly suggests the therapeutic potential of cystamine in SLE.

Key Words: systemic lupus erythematosus (SLE) • matrix metalloproteinase (MMP) • transglutaminase 2 (TG2) • cystamine

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