Sato K, Fujihara M, Takahashi T A, Choon Yoo Y, Hata K, Tono-Oka S, Suzuki T, Sekiguchi S, Azuma I
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Biochem Biophys Res Commun. 1995 Nov 2;216(1):367-74. doi: 10.1006/bbrc.1995.2633.
We examined the molecular mechanism of DT-5461-induced LPS antagonism in human peripheral blood monocytes. Dose-response studies revealed that LPS-induced IL-1 and TNF-alpha production was apparently totally suppressed in a competitive manner by a 10-fold excess of DT-5461. A 10-fold excess of DT-5461 significantly blocked the binding of FITC-LPS to the monocytes. DT-5461 suppressed IL-1 and TNF-alpha mRNA expression in LPS-activated monocytes. Western blots showed that DT-5461 suppressed the LPS-induced tyrosine phosphorylation of p42mapk/ERK2. These results suggested that the competitive binding inhibition and repression of early intracellular signaling involved in DT-5461-mediated LPS antagonism.
