(a) Key role of the signaling pathway on LMP2 expression. (b) Immunohistochemical
experiments with myometrium tissue sections derived from wild-type, IFN-γ-deficient, and
TNF-α-deficient mice (2 months old) were carried out. (magnification x100) The results
revealed that the IFN-γ signaling cascade was required for basal LMP2 expression. (c)
Western blotting and RT-PCR experiments with myometrium tissue sections derived from
wild-type and IFN-γ- and TNF-α-deficient mice (2 months old) were also performed. The
results showed that IFN-γ-deficient mice had markedly reduced LMP2 levels in myometrium
tissues. These findings support the notion that the IFN-γ pathway plays a key role in
basal LMP2 expression. (d) Schematic representation of the LMP2/TAP1 bidirectional
promoter, including NF-κB and IRF-1 binding sites. Chromatin immunoprecipitation (ChIP)
analysis with antibodies against RelA (NF-κBp65) and IRF-1 was carried out. (e) ChIP
assays showing that although mouse genomic DNA of the Lmp2 enhancer/promoter
region was markedly amplified using immunoprecipitated TNF-α-deficient myometrium tissue
with anti-IRF-1 antibody, amplified products were not detected using immunoprecipitated
IFN-γ-deficient myometrium tissue with anti-IRF-1 antibody. The mouse genomic DNA of the
LMP2 enhancer/promoter region was unclearly amplified using the immunoprecipitated
materials with anti-RelA antibody. Positive control (P.C.): IFN-γ-treated mouse
embryonic fibroblasts (lane 6), TNF-α-treated mouse splenocytes (lane 11). (f) ChIP
assays showing that although human genomic DNA of the LMP2 enhancer/promoter region was
markedly amplified using immunoprecipitated LMA tissue as well as normal myometrium
tissue with anti-IRF-1 antibody, no-DNA amplification was detected in the
immunoprecipitated LMS sample with anti-IRF-1 antibody. The DNA of the LMP2
enhancer/promoter region was not clearly amplified using any immunoprecipitated
myometrium tissue materials with anti-RelA antibody. Positive control (P.C.):
IFN-γ-treated mouse embryonic fibroblasts (lane 6), TNF-α-treated mouse splenocytes
(lane 11). N.IgG, normal rabbit anti-serum was used as a negative control antibody. The
experiments were performed four times with similar results.