Mycoplasmal lipoproteins induce toll-like receptor 2- and caspases-mediated cell death in lymphocytes and monocytes.
Lipoproteins of Mycoplasma salivarium and Mycoplasma fermentans preferentially induced necrotic cell death in lymphocytic cell lines, MOLT-4 and Raji, and in one monocytic cell line, THP-1, whereas they preferentially induced apoptotic cell death in another monocytic cell line, HL-60. These findings were also supported by ultrastructural observations by the use of scanning and transmission electron microscopes and by agarose gel electrophoresis of the genomic DNA. The lipoproteins activated caspase-3 in both MOLT-4 and HL-60 cells, which was assessed by the cleavage of the synthetic substrate DEVD-pNA and the endogenous substrate poly(ADP-ribose) polymerase. The cytotoxicity to MOLT-4 and HL-60 cells was inhibited by various caspase inhibitors, Ac-DMQD-CHO, Ac-IETD-CHO, and Z-VAD-FMK. The cytotoxicity was also partially suppressed by the monoclonal antibody to Toll-like receptor 2. Thus this study demonstrated that mycoplasmal lipoproteins induce caspases-dependent necrotic and apoptotic cell death in lymphocytes and monocytes/macrophages, which is partially induced by TLR2-mediated signaling.
Into
Takeshi
T
Department of Oral Pathobiological Science and Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan.
Nodasaka
Yosinobu
Y
Hasebe
Akira
A
Okuzawa
Tsugumi
T
Nakamura
Jun-ichiro
J
Ohata
Noboru
N
Shibata
Ken-ichiro
K
D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D029721:Drosophila Proteins; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology; D009174:Mycoplasma / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D061945:Caspase Inhibitors; D029721:Drosophila Proteins; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases