The transcription factor IFN regulatory factor–4 controls experimental colitis in mice via T cell–derived IL-6
J. Clin. Invest. Jonas Mudter, et al. 118:2415 doi:10.1172/JCI33227 [Go to this article.]

Figure 7
Hyper–IL-6 treatment induces IL-6 but not TNF production in IRF4^–/– mice. (A) WT and IRF4-knockout mice were treated with TNBS, and some mice received hyper–IL-6. Relative expression levels of IL-6, TNF, and TGF-β mRNA were measured by quantitative real-time RT-PCR on day 4. Values were normalized to β-actin expression levels. TNBS-treated IRF4^–/– mice (n = 8) showed low mucosal expression of IL-6 mRNA. Hyper–IL-6 application induced a 14-fold increase of IL-6 production in TNBS-treated IRF4^–/– mice (n = 6) (**P < 0.01). The expression levels of the proinflammatory cytokine TNF as well as levels of TGF-β remained unaffected, however. Treatment of WT mice with hyper–IL-6 (n = 5; WT mice, n = 4) did not lead to a further significant increase of IL-6, TNF, or TGF-β. Data are shown as mean values ± SEM from 3 experiments. (B and C) IRF4-knockout mice and WT mice were treated with TNBS, and the presence of apoptosis in gut mononuclear cells was determined by propidium iodide and annexin V staining using FACS analysis (n = 6 per group). IRF4-deficient mononuclear cells in the gut showed a significantly higher presence of cell apoptosis in TNBS colitis than in WT cells, and this could be abrogated by hyper–IL-6 administration. One representative experiment is shown. *P < 0.05. (D) Apoptosis of gut mononuclear cells was determined by TUNEL assays. Hyper–IL-6 treatment prevented the induction of mononuclear cell apoptosis in the colon of IRF4-deficient mice. One representative experiment is shown (n = 4 per group). Original magnification, ×300.