Redundant roles for cJun-N-terminal kinase 1 and 2 in interleukin-1beta-mediated reduction and modification of murine hepatic nuclear retinoid X receptor alpha.

Background/aims: Retinoid X receptor alpha (RXRalpha), the heterodimeric partner for multiple nuclear receptors (NRs), was shown to be an essential target for inflammation-induced cJun-N-terminal kinase (JNK) signaling in vitro. This study aimed to explore the role of hepatic JNK signaling and its effects on nuclear RXRalpha levels downstream of interleukin-1beta (IL-1beta) in vivo.

Methods: Effects of IL-1beta on hepatic NR-dependent gene expression, nuclear RXRalpha levels, and roles for individual JNK isoforms were studied in wild-type, Jnk1(-/-), and Jnk2(-/-) mice and in primary hepatocytes of each genotype.