ono-4057 and Pulmonary-Fibrosis

ono-4057 has been researched along with Pulmonary-Fibrosis* in 2 studies

Other Studies

2 other study(ies) available for ono-4057 and Pulmonary-Fibrosis

ArticleYear
Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis.
    The European respiratory journal, 2009, Volume: 34, Issue:6

    Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Leukotrienes play an important role in IPF, and leukotriene (LT)B(4) is one of the key eicosanoids in IPF. In this study, we investigated whether ONO-4057, a LTB(4) receptor (BLTR) antagonist is capable of preventing bleomycin-induced pulmonary fibrosis. On day 1, C57BL/6 male mice were given a single intratracheal injection of bleomycin (2.5 mg x kg(-1)), and ONO-4057 (1.0 mg x kg(-1)) or vehicle alone, administered by intraperitoneal injection on days 1-5 each week for 3 weeks after the bleomycin injection. ONO-4057 reduced the total cell count in bronchoalveolar lavage fluid (BALF) on days 7, 14 and 21 and the Ashcroft score and the lung hydroxyproline content on days 14 and 21. The LTB(4), interleukin (IL)-6, IL-13, transforming growth factor (TGF)-beta levels in BALF and the TGF-beta expression in lung tissue, assessed by immunohistochemistry were decreased on day 7, whereas interferon (IFN)-gamma level in BALF was increased on day 14. The results of this study indicated that the BLTR antagonist inhibited the development of bleomycin-induced pulmonary fibrosis in mice by decreasing inflammation and altering TGF-beta, IL-6, IL-13 and IFN-gamma.

    Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Bronchoalveolar Lavage Fluid; Immunohistochemistry; Immunosuppressive Agents; Interferon-gamma; Interleukin-13; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Phenylpropionates; Prognosis; Pulmonary Fibrosis; Receptors, Leukotriene B4; Transforming Growth Factor beta

2009
Smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities.
    The American journal of physiology, 1999, Volume: 277, Issue:6

    Accumulation of monocytes and neutrophils and fibrous distortion of the airway are characteristics of airway disease secondary to smoking. The presence of inflammatory cells and fibrosis correlate, and, therefore, we postulated that lung fibroblasts might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, human fetal lung (HFL1) fibroblasts were cultured, and the supernatant fluid was evaluated for neutrophil (NCA) and monocyte (MCA) chemotactic activities with a blind well chamber technique. HFL1 fibroblasts released chemotactic activity in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was predominantly chemotactic. Partial characterization of the released chemotactic activity revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of both NCA and MCA. Molecular-sieve chromatography revealed that NCA and MCA were heterogeneous. NCA was inhibited by anti-human interleukin (IL)-8 and anti-granulocyte colony-stimulating factor antibodies and a leukotriene (LT) B(4)-receptor antagonist. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-monocyte chemoattractant protein (MCP)-1 antibodies and an LTB(4)-receptor antagonist inhibited MCA. Immunoreactive IL-8, granulocyte colony-stimulating factor, GM-CSF, and MCP-1 significantly increased in culture supernatant fluid in response to smoke extract. Finally, smoke extract augmented the expression of mRNAs of IL-8, GM-CSF, and MCP-1. These data demonstrate that lung fibroblasts release NCA and MCA in response to smoke extract and suggest that lung fibroblasts may modulate the inflammatory cell recruitment into the lung.

    Topics: Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Chemotaxis; Chromatography; Cycloheximide; Fibroblasts; Gene Expression; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Interleukin-8; Isoquinolines; Leukotriene B4; Lung; Monocytes; Neutrophils; Nicotiana; Phenylpropionates; Plants, Toxic; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Protein Synthesis Inhibitors; Pulmonary Fibrosis; Pyridinium Compounds; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Smoking; Tetrahydroisoquinolines; Transforming Growth Factor beta

1999