Cloricromene decreases myocardial infarct size after ischemic-reperfusion injury in vivo, and it has been suggested that this is due to inhibition of tumor necrosis factor-α (TNF-α). The purpose of this work was to characterize the mechanism of cloricromene-induced inhibition of TNF-α in rat macrophages. Cloricromene inhibited lipopolysaccharide-induced TNF-α release in a dose-dependent manner (IC 50 = 5.9 ± 0.8 μM). This was not due to cytotoxicity, as cloricromene was well tolerated up to 500 μM. Cloricromene inhibited lipopolysaccharide-induced expression of TNF-α mRNA, which suggests a pre-transcriptional effect. We then investigated the early signal transduction pathway triggered by lipopolysaccharide. The binding of lipopolysaccharide to its receptor CD14 activates protein kinase C and nuclear factor-κB (NF-κB). Cloricromene inhibited NF-κB activation in a dose-dependent manner, but affected protein kinase C translocation only slightly. We then established that cloricromene inhibited lipopolysaccharide-induced cellular oxidative activity, which is important for NF-κB activation. Our results show that cloricromene interferes with the early signal transduction pathway triggered by lipopolysaccharide.
Cloricromene, a semi-synthetic coumarin derivative, inhibits tumor necrosis factor-α production at a pre-transcriptional level / E. Corsini, L. Lucchi, M. Binaglia, B. Viviani, C. Bevilacqua, G. Monastra, M. Marinovich, C.L. Galli. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 418:3(2001), pp. 231-237.
|Titolo:||Cloricromene, a semi-synthetic coumarin derivative, inhibits tumor necrosis factor-α production at a pre-transcriptional level|
CORSINI, EMANUELA (Primo)
LUCCHI, LAURA (Secondo)
MARINOVICH, MARINA (Penultimo)
GALLI, CORRADO LODOVICO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2001|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S0014-2999(01)00910-4|
|Appare nelle tipologie:||01 - Articolo su periodico|