Transforming growth factor-beta induces apoptosis in activated murine T cells through the activation of caspase 1-like protease.
Transforming growth factor-beta (TGF-beta) has been known as a potent immunosuppressive cytokine that can induce apoptosis in lymphoid cells. We established an IL-2-independent cell line, CTLL-2A, from murine T cell line CTLL-2. CTLL-2A expressed higher levels of CD95, CD69, and CD18 molecules than CTLL-2 did, suggesting a more activated state in CTLL-2A than in the CTLL-2 by phenotype. Exposing both CTLL-2 and CTLL-2A to TGF-beta results in differential apoptosis patterns defined by DNA fragmentation and plasma membrane alteration. Among the bcl-2 family members, bcl-2, bcl-w, and bcl-x(L) were also differently expressed in these two cell lines. In CTLL-2A, bcl-x(L) was amplified as a major anti-apoptotic molecule, and TGF-beta-induced cell death was more enhanced than in the original cell line. Caspase 1-like protease was activated by TGF-beta treatment and consequently it cleaved bcl-x(L) in CTLL-2A. TGF-beta-induced DNA fragmentation and cleavage of bcl-x(L) were inhibited by pretreatment with tetra peptide caspase 1 inhibitor, YVAD.cmk. These findings suggest that TGF-beta induces cell death in activated murine T cells through cleavage of bcl-x(L) via activated caspase 1-like protease, which may act as an important executor in that process.
Chung
E J
EJ
Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Choi
S H
SH
Shim
Y H
YH
Bang
Y J
YJ
Hur
K C
KC
Kim
C W
CW
D000818:Animals; D017209:Apoptosis; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3; D061945:Caspase Inhibitors; D002460:Cell Line; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D061945:Caspase Inhibitors; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D051020:bcl-X Protein; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020170:Caspase 1