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.
Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Tomoki
T
Chiba
Keiko
K
Miyashita
Tatsuya
T
Sugoh
Takayuki
T
Warita
Hidetoshi
H
Inoko
Minoru
M
Kimura
Takehito
T
Sato
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism
D016207:Cytokines; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D019913:Nuclear Localization Signals; D020033:Protein Isoforms