Beneficial effects of treatment with transglutaminase inhibitor cystamine on macrophage response in NZB/W F1 mice.
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 F(1) 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 F(1) mice following cystamine administration. It strongly suggests the therapeutic potential of cystamine in SLE.
Hsu
Tsai-Ching
TC
Institute Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Chiang
Szu-Yi
SY
Huang
Chih-Yang
CY
Tsay
Gregory J
GJ
Yang
Chiao-Wen
CW
Huang
Chien-Ning
CN
Tzang
Bor-Show
BS
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000235:genetics; D001483:Base Sequence; D003538:Cystamine / Q000494:pharmacology*; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008264:Macrophages / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D011503:Transglutaminases / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D017153:Antibodies, Anticardiolipin; D017931:DNA Primers; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D011503:Transglutaminases; D020780:Matrix Metalloproteinase 9; D003538:Cystamine