Figure 4

Joint IFN-γ and IL-1β production via TLR4-mediated IL-12 production suppresses TGF-β production, thereby promoting antibody-induced arthritis. (A) Toll-like receptor (TLR)4^-/- mice were injected intraperitoneally (i.p.) with recombinant interleukin (IL)-12, IL-1β (500 ng in 300 μL of PBS), interferon (IFN)-γ (400 ng in 300 μL of phosphate-buffered saline (PBS)) or anti-transforming growth factor (TGF)-β1 mAb (100 μg in 300 μL of PBS), one and three days prior to, and one day after K/BxN serum transfer (150 μL, twice). Clinical scores and ankle thickness were monitored in these mice and compared with those in TLR4^-/- and wild type (WT) mice (n = 4). (B) IFN-γ, TGF-β, IL-12p35 and IL-1β transcript levels were measured in the joint tissues of WT and TLR4^-/- mice, and TLR4^-/- mice injected with recombinant IL-12, IL-1β, IFN-γ or anti-TGF-β1 mAb (n = 4). The results shown are representative of three repeated independent experiments. n.s., not significant; * P < 0.05, ** P < 0.01, *** P < 0.001.