Newly identified NBD mimetics suppress LPS-induced acute inflammation in vivo.

<p>(A) The bioavailability property of SR12460, SR12343, SR12454, and SR11481. Concentrations of NBD mimetics were determined in plasma, brain, muscle, spleen, and liver 2 h post a single i.p. injection of 10 mg/kg of drugs; <i>n</i> = 3 per group. (B) Shown is the model to induce LPS-mediated acute inflammation and the treatment regimen with NBD mimetics. Mouse image via <a href="http://www.clker.com/clipart-mice-blank.html" target="_blank">http://www.clker.com/clipart-mice-blank.html</a> (copyright-free). (C) NBD mimetics suppressed LPS-induced acute inflammation in liver and lung by down-regulating NF-κB target gene expression. Vehicle, SR12343, SR12460, and 8K-NBD peptide were dosed at 10 mg/kg 30 min prior to the LPS treatment. Acute inflammation was induced by i.p. injection of 10 mg/kg LPS. Lung and liver were collected 2–4 h post injection, and mRNA was extracted for qRT-PCR analysis. (D, E) Western blot analysis was performed to probe for the expression of p-IκBα and COX-2 at protein level in liver and lung tissues. (F) Serum levels of IL-6 were determine by ELISA. <i>n</i> = 3–8 each group. *<i>P</i> < 0.05, **<i>P</i> < 0.01. Underlying data can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004663#pbio.2004663.s001" target="_blank">S1 Data</a>. COX-2, cyclooxygenase 2; IL-6, interleukin 6; i.p., intraperitoneal; LPS, lipopolysaccharide; NBD, NEMO-binding domain; n.d., nondetectable; NEMO, NF-κB essential modulator; NF-κB, nuclear factor κB; qRT-PCR, quantitative real-time polymerase chain reaction.