IκBL, a novel member of the nuclear IκB family, inhibits inflammatory cytokine expression

We previously reported that IκBL prevents experimental autoimmune arthritis. The molecular mechanism, however, still remains unclear. In contrast to four splicing-isoforms of IκBL in human, two isoforms were identified in mouse. The major isoform IκBL-α(S) suppressed LPS-induced NF-κB activation and transcription of TNFα and IL-6, but not IL-1β. The suppressive activity required the nuclear localization signal and the ankyrin repeat domain of IκBL. IκBL did not affect the nuclear translocation of the NF-κB dimer. These findings point to IκBL as being a novel member of the nuclear IκB family, which functions in the nucleus and controls various inflammatory responses including autoimmune arthritis.

► Two isoforms of IκBL were identified in mouse cells. ► IκBL showed suppressive effects on NF-κB and inflammatory cytokine expressions. ► IκBL’s nuclear localization signal and ankyrin repeat were required for the activity. ► NFκB activation cascade in the cytoplasm was not influenced by IκBL. ► These findings suggested that IκBL is a novel member of the nuclear IκB.