title: Inhibited proliferation of human lung fibroblasts by LPS is through IL-6 and IL-8 release.
abstract: Through the consideration of decreased proliferation of lung fibroblasts from subjects with chronic obstructive pulmonary disease (COPD) and the proinflammatory role of lipopolysaccharide (LPS) in the COPD development, we hypothesized that LPS might inhibit proliferation in lung fibroblasts and the possible mechanism was investigated. Primary human lung fibroblasts were cultured from peripheral lung tissue and then treated with or without LPS. Proliferation was measured by AlamarBlue® assay. Levels of TNF-α, IL-6, IL-8, IL-12p70, IL-1β and IL-10 in the supernatants were measured by ELISA. The mRNA of histone deacetylases 2 (HDAC2) was analyzed using real-time PCR. LPS appeared to have a dose-dependent inhibitory effect on fibroblasts proliferation. The concentrations of IL-6 and IL-8 in the treatment culture media were significantly increased, accompanied by a reduced mRNA expression of HDAC2. IL-6 or IL-8 itself led to the reduction of fibroblasts proliferation. Treatment with 1 ng/ml TNF-α in fibroblasts also caused a significant decrease in proliferation and an increase in the production of IL-8 and IL-6. Our data suggest that LPS can inhibit the proliferation of in vitro human lung fibroblasts at least through a production of IL-6 and IL-8. The cytokine response is related to the decreased HDAC2 transcription.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Lian
authors.initials: L
authors.lastname: Wu
authors.forename: Jie-Ming
authors.initials: JM
authors.lastname: Qu
mesh_terms: D049109:Cell Proliferation; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2