TY - JOUR T1 - Taurine and Niacin Block Lung Injury and Fibrosis by Down-Regulating Bleomycin-Induced Activation of Transcription Nuclear Factor-κB in Mice <span class="xref-sep">,</span> JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 82 LP - 90 VL - 293 IS - 1 AU - Gopalakrishnan Gurujeyalakshmi AU - Yingjin Wang AU - Shri N. Giri Y1 - 2000/04/01 UR - http://jpet.aspetjournals.org/content/293/1/82.abstract N2 - The effects of taurine (T) and niacin (N) on bleomycin (BL)-induced increased production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1α, IL-6, and transforming growth factor-β (TGF-β) levels in the bronchoalveolar lavage fluid (BALF), and increased collagen content and nuclear factor-κB (NF-κB) activation in the lungs were investigated in mice. The mice were intratracheally instilled with saline (SA) or BL (0.1 U/mouse/50 μl) under ketamine and xylazine anesthesia. They had ad libitum access to diet containing 2.5% niacin (w/w) or the same control diet (CD) and water with and without taurine (1%) 3 days before intratracheal instillation and throughout the study. The mice were sacrificed at different times for collecting BALF and lungs, which were appropriately processed for various measurements. Treatment with taurine and niacin attenuated the BL-induced increases in proinflammatory cytokines such as IL-1α, TNF-α, IL-6, and TGF-β in BALF and lung hydroxyproline content of the mice in BL + TN groups. Reverse transcription-polymerase chain reaction analysis of total RNA from whole lung was performed to assess the induction of TNF-α and IL-1 mRNAs as markers of NF-κB activation. The NF-κB DNA-binding activity in whole-lung extract was evaluated by electrophoretic mobility shift assay. This revealed a progressive increase in NF-κB activation and IkBα depletion in lungs from mice in BL + CD groups from day 1 through day 21 compared with the corresponding SA + CD control groups. Treatment with taurine and niacin generally inhibited the BL-induced increases in the nuclear localization of NF-κB and preserved IκBα protein in BL + TN groups. This may be one of the mechanisms for the antifibrotic effect of taurine and niacin. The American Society for Pharmacology and Experimental Therapeutics ER -