Cytotoxic effect of triptolide on LPS-treated macrophages through sustained phosphorylation of p38 MAP kinase and apoptosis

Kiyoko Kohama, Atsushi Koike, Fumio Amano


Triptolide induced the death of cells of lipopolysaccharide (LPS)- treated macrophage-like cell line J774.1/JA-4 cells through apoptosis but not through activation during incubation at 37oC for 4 h. This phenomenon was dependent on the dose and the time of addition of triptolide; and prior or simultaneous addition to LPS was needed, suggesting mal-regulation of LPS-signaling cascades. LPS rapidly induced phosphorylation of p38 MAP kinase, JNK and Erk1/2 within 15 min of its addition, and then dephosphorylation of them followed by 60 min. However, the addition of triptolide, but not endothall, inhibited this dephosphorylation of phospho-p38 and phosphor-JNK in these cells, suggesting that MKP-1 was involved in the dephosphorylation of these phosphoproteins. Triptolide inhibited the synthesis of MKP-1 mRNA and protein induced by LPS. Compared with our previous studies, where a protein synthesis inhibitor, cycloheximide (CHX), induced rapid apoptotic cell death in LPS-treated macrophages through sustained phosphorylation of p38, triptolide seemed to induce cell death of LPS-treated macrophages by inhibition of MKP-1 induction.


macrophage cell death; triptolide; lipopolysaccharide (LPS); p38 MAP kinase; phosphorylation, apoptosis, MKP-1

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DOI: http://dx.doi.org/10.18103/ibr.v1i2.1399


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