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- Title
Stimulation of human Toll-like receptor (TLR) 2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-κB activation.
- Authors
Takeshi Into, I. B.; Kazuto Kiura, I. B.; Motoaki Yasuda, I. B.; Hideo Kataoka, I. B.; Nobuo Inoue, I. B.; Akira Hasebe, I. B.; Kiyoshi Takeda; Shizuo Akira, I. B.; Ken-ichiro Shibata, I. B.
- Abstract
Mycoplasmal membrane diacylated lipoproteins not only initiate proinflammatory responses through Toll-like receptor (TLR) 2 and TLR6 via the activation of the transcriptional factor NF-κB, but also initiate apoptotic responses. The aim of this study was to clarify the apoptotic machineries. Mycoplasma fermentans lipoproteins and a synthetic lipopeptide, MALP-2, showed cytocidal activity towards HEK293 cells transfected with a TLR2-encoding plasmid. The activity was synergically augmented by co-expression of TLR6, but not by co-expression of other TLRs. Under the condition of co-expression of TLR2 and TLR6, the lipoproteins could induce maximum NF-κB activation and apoptotic cell death in the cells 6 h and 24 h after stimulation respectively. Dominant-negative forms of MyD88 and FADD, but not IRAK-4, reduced the cytocidal activity of the lipoproteins. In addition, both dominant-negative forms also downregulated the activation of both NF-κB and caspase-8 in the cells. Additionally, the cytocidal activity was sufficiently attenuated by a selective inhibitor of p38 MAPK. These findings suggest that mycoplasmal lipoproteins can trigger TLR2- and TLR6-mediated sequential bifurcate responses: NF-κB activation as an early event, which is partially mediated by MyD88 and FADD; and apoptosis as a later event, which is regulated by p38 MAPK as well as by MyD88 and FADD.
- Subjects
MYCOPLASMA; APOPTOSIS; NF-kappa B; TRANSCRIPTION factors; LIPOPROTEINS; CELL death
- Publication
Cellular Microbiology, 2004, Vol 6, Issue 2, p187
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1046/j.1462-5822.2003.00356.x