Overexpression of Tumor Necrosis Factor-α Diminishes Pulmonary Fibrosis Induced by Bleomycin or Transforming Growth Factor-β
ABSTRACT Tumor necrosis factor-alpha (TNF-alpha) is thought to be important in the development of pulmonary fibrosis. However, surfactant protein-C/TNF-alpha transgenic mice do not spontaneously develop pulmonary fibrosis but instead develop alveolar enlargement and loss of elastic recoil. We hypothesized that overexpression of TNF-alpha in the lung requires an additional insult to produce fibrosis. In this study we evaluated whether TNF-alpha overexpression altered the development of pulmonary fibrosis due to bleomycin or transforming growth factor-beta (TGF-beta). Either 0.2 U bleomycin or saline was administered into left lung of TNF-alpha transgenic mice and their transgene-negative littermates. To overexpress TGF-beta, an adenovirus vector containing either active TGF-beta (AdTGF-beta) or LacZ was administered at a dose of 3 x 108 plaque-forming units per mouse. Fibrosis was assessed histologically and by measurement of hydroxyproline. TNF-alpha transgenic mice tolerated bleomycin or AdTGF-beta, whereas the transgene-negative littermates demonstrated severe pulmonary fibrosis after either agent. An increase in prostaglandin E2 and downregulation of TNF receptor I expression were observed in the TNF-alpha transgenic mice. In addition, recombinant human TNF-alpha attenuated bleomycin-induced pulmonary fibrosis. TNF-alpha has a complex role in the development of pulmonary fibrosis. Endogenous TNF-alpha may be important in the development of fibrosis as indicated in other reports, but overexpression of TNF-alpha or exogenous TNF-alpha limits pulmonary fibrosis in mice.
- SourceAvailable from: Jong Suk Lee
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- "MDA is a biomarker for lipid peroxidation generated by ROS, which are critically controlled by NOX, the reduced form of NADPH oxidase (Cui et al., 2011; Levitan et al., 2010). NO is a typical indicator of reactive oxygen species (ROS), and lipid peroxidation is an indicator of oxidative stress in the BDL model (Alptekin et al., 1997; Desmet et al., 1995; Fujita et al., 2003). Immunochemistry staining against 4-HNE demonstrated the lipid peroxidation inside cells (Poli and Schaur, 2000), and BDL treatment strongly enhanced the 4-HNE expression compared to the sham group. "
ABSTRACT: Artemisia capillaris has been widely used as a traditional herbal medicine in the treatment of liver diseases. However, no previous study has investigated whether A. capillaries alone is effective in treating pathological conditions associated with cholestatic liver injury. In the present study, we evaluated the anti-hepatofibrotic effects of A. capillaris (aqueous extract, WAC) in a bile duct ligation (BDL)-induced cholestatic fibrosis model. After BDL, rats were given WAC (25 or 50mg/kg) or urosodeoxycholic acid (UDCA, 25mg/kg) orally for 2 weeks (once per day). The serum cholestatic markers, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group, while administering WAC significantly reduced these alterations. Administering WAC also restored the BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAC treatment, and these changes were paralleled by the significantly suppressed expression of fibrogenic factors, including hepatic alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-β). The beneficial effects of WAC administration are associated with antifibrotic properties via both upregulation of antioxidant activities and downregulation of ECM protein production in the rat BDL model.Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 01/2013; 65(6). DOI:10.1016/j.etp.2012.12.002 · 2.01 Impact Factor
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- "About 0.1 G tissues was digested in 2ml conc Nitric acid and 2 ml perchloric acid at room temperature for 24 hours, the samples were filtered, diluted and absorption was measured at 248 nm. Hyp was determined spectrophotometrically by Ehrlich reagent . 0.1 G tissues was pulverized ground, 500 ul of 6 N Hcl were added and incubated overnight at 120 c. 5 ul of acid hydrolysate were mixed with 5 ul of citrate acetate buffer and 100 ul chloramines T in ELISA plate and incubated for 20 minutes at room temperature before addition of Ehrlich solution. "
ABSTRACT: Iron deficiency anemia represents a common nutritional problem which affects many socie-ties allover the world and iron fortified diet has been suggested as one of possible tools to combat and solve such problem. Present study was designed to illustrate the effect of dietary iron intake on certain biochemical markers dealing with oxidative stress, inflammatory re-sponse and cellular alterations of testicular tissues. Adult male rats which were fed on bis-cuits fortified with iron (0.3% ferrous sulfate) daily for 10 weeks (iron group) showed increa-sed serum iron, ferritin, tumor necrosis factor-alpha (TNF-α), nitric oxide (NO) and decreased Testosterone level (p < 0.05). Testicular tissues content of Malondialdehyde (MDA), hydroxypro-line (Hyp), iron showed significant increase (p < 0.05) and decreased glutathione (GSH) as com-pared to control group. Testicular tissues dem-onstrated massive iron distribution in sertoli interstial tissues and degeneration of germinal epithelial cells. Apparent reduction in number of sperms and spermatogenic cells were also obs-erved. These symptoms may demonstrate that prolonged intake of Biscuit fortified with iron causes certain testicular damage through cert-ain mechanism.Natural Science 01/2010; 2(06):551-556. DOI:10.4236/ns.2010.26069
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- "Analysis of inflammatory cell profile of bronchoalveolar lavage fluid (BALF). Bronchoalveolar lavage was performed through a tracheal cannula with PBS (PH 7.4) as previously described (Fujita et al., 2003). This was repeated four times. "
ABSTRACT: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the ligand-activated nuclear receptor superfamily, has been shown to be implicated in anti-inflammatory and immunomodulatory responses, but its role in airway mucus hypersecretion remains not clear. To investigate the role of PPAR-gamma in airway mucus hypersecretion, we used an acrolein-exposed rat model treated with rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist. Rats were exposed to acrolein (3.0 ppm, 6h/day, 7 days/week) and orally administered with rosiglitazone (2, 4, 8 mg/kg) once daily for up to 2 weeks. The expressions of Muc5ac protein and mRNA, and infiltration of inflammatory cells and levels of inflammatory cytokines (interleukin (IL)-1beta, IL-8 and tumor necrosis factor (TNF)-alpha) in bronchoalveolar lavage fluid (BALF) were detected with real-time PCR, Western blot, cell counting and ELISA. In addition, the role of nuclear factor (NF)-kappaB pathway in this process was also explored. Acrolein exposure significantly induced goblet cell hyperplasia in bronchial epithelium and Muc5ac mRNA and protein expressions in rat lungs, as well as the associated airway inflammation evidenced by the increased numbers of inflammatory cells and levels of inflammatory cytokines in BALF, which were attenuated with rosiglitazone treatment in a dose-dependent manner (P<0.05). Simultaneously, the increased expression of NF-kappaB and decreased expression of cytoplasmic IkappaB in acrolein-exposed lungs were reversed by rosiglitazone treatment. These findings suggest that PPAR-gamma activation by its ligands can attenuate acrolein-induced airway mucus hypersecretion in rats, which may be involved in inhibition of NF-kappaB pathway.Toxicology 06/2009; 260(1-3):112-9. DOI:10.1016/j.tox.2009.03.016 · 3.75 Impact Factor