title: Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice.
abstract: It is well known that the intake of paraquat (PQ), an herbicide, causes severe lung injury at chronic phases. We examined the intrapulmonary gene expression of cytokines and growth factors after PQ administration. To induce lung injury, C57BL/6 mice were intraperitoneally injected twice a week with 20 mg/kg of PQ. Histopathologically, at the early phase, lots of alveolar spaces contained edematous fluid. At 3 weeks after PQ challenge, a marked thickening of the alveolar walls with the accumulation of macrophages and T cells was found. Azan staining revealed the patchy distribution of collagen accumulation, indicating pulmonary fibrosis. Consistently, intrapulmonary hydroxyproline contents were significantly elevated, compared with the controls. Semi-quantitative RT-PCR analysis demonstrated that the gene expression of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly increased at 3 weeks after PQ challenge compared with the controls. The mRNA expression of macrophage inflammatory protein (MIP)-1alpha and MIP-2 was significantly enhanced at 1 and 2 weeks after PQ treatment, respectively. Moreover, PQ-treated mice showed enhanced gene expression of fibrogenic growth factors such as transforming growth factor-beta, platelet-derived growth factor-A, acidic fibroblast growth factor, and hepatoctyte growth factor at 2 and/or 3 weeks after PQ challenge. The synergistic effects of these molecules are presumed to cause pulmonary fibrosis due to PQ challenge.
authors.affiliation: Department of Forensic Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan. iyuko@wakayama-med.ac.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishida
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Takayasu
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kimura
authors.forename: Takahito
authors.initials: T
authors.lastname: Hayashi
authors.forename: Nobuyuku
authors.initials: N
authors.lastname: Kakimoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyashita
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D049429:Forensic Pathology; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006540:Herbicides / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010269:Paraquat / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D016207:Cytokines; D006133:Growth Substances; D006540:Herbicides; D012333:RNA, Messenger; D003094:Collagen; D010269:Paraquat; D006909:Hydroxyproline