Abstract
Numerous microbial as well as other stimulants including lipopolysaccharide and taxol can activate TLR4, and elicit diverse downstream signaling events including cytokine gene expression and cell growth regulation. With a mechanism not completely understood, different TLR4 stimulants induce distinct cellular responses. Our present studies showed that taxol, not LPS, induced cell apoptosis in human monocytic THP-1 cells, as indicated by PARP cleavage, as well as bcl-2 phosphorylation. Pretreatment of cells with LPS abolished subsequent taxol effect, suggesting that certain signaling components involved in taxol-mediated apoptosis were disrupted by LPS pretreatment. Since the decrease in IRAK-1 level closely accompanies prolonged LPS treatment in monocytic cells, we investigated the IRAK-1 status upon various taxol and LPS challenges. We observed that only LPS, not taxol, caused dramatic decrease in IRAK-1 protein levels. Using splenic macrophages harvested from IRAK-1 knockout and control mice, we further demonstrated that the presence of IRAK-1 is required for taxol-induced PARP cleavage.
Original language | English (US) |
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Pages (from-to) | 1049-1055 |
Number of pages | 7 |
Journal | Molecular Immunology |
Volume | 42 |
Issue number | 9 |
DOIs | |
State | Published - May 2005 |
Keywords
- Apoptosis
- IRAK-1
- Innate immunity
- Signaling
- THP-1 cells
- Taxol
ASJC Scopus subject areas
- Immunology
- Molecular Biology