title: Differential induction of apoptosis by LPS and taxol in monocytic cells.
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.
authors.affiliation: Section of Molecular Medicine, Department of Medicine, Wake Forest, University School of Medicine, Winston Salem, NC 27157, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jean
authors.initials: J
authors.lastname: Hu
authors.forename: James A
authors.initials: JA
authors.lastname: Thomas
authors.forename: Liwu
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D017472:Receptors, Interleukin-1; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; D017239:Paclitaxel