Gene

Kinase

Caspase 3

NF-κB

Programmed cell death

Cell biology

Biology

Regulator

Lipopolysaccharide

Apoptosis

Signal transduction

Biochemistry

Caspase 1

Phosphorylation

IκB kinase

Immunology

Caspase 8

Caspase

Inflammation

Transcription factor

Proinflammatory cytokine

Chemistry

Cell Death and Differentiation

Caspase-11 is a key regulator of proinflammatory cytokine IL-1beta maturation and pathological apoptosis. Caspase-11 is not expressed in most tissues under normal condition, but highly inducible upon pathological stimulation such as in the presence of lipopolysaccharide (LPS). Here, we describe the identification and characterization of wedelolactone, a natural compound that inhibits LPS-induced caspase-11 expression in cultured cells by inhibiting NF-kappaB-mediated transcription. We demonstrate that wedelolactone is an inhibitor of IKK, a kinase critical for activation of NF-kappaB by mediating phosphorylation and degradation of IkappaBalpha.

Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK Complex