title: Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure.
abstract: Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic interstitial lung diseases characterized by alveolar wall fibrosis with accumulation of extracellular matrix, interstitial remodeling, and increased numbers of activated alveolar macrophages. Animal models and in vitro studies have shown that macrophage cytokines, namely IL-1 beta and TNF-alpha, play significant roles in the development of fibrosis. We found significant increases for TNF-alpha release in both diseases (p < 0.01) and a significant increase for IL-1 beta release in asbestosis compared to normal controls (p < 0.01). Also, the mRNA expression of these cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha release in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, crocidolite, amosite asbestos, and silica stimulated IL-1 beta and TNF-alpha release and up-regulated their respective mRNA in macrophages or monocytes. To evaluate the role of IL-1 beta and TNF-alpha in the accumulation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after short term (2 h) serum-free exposure to recombinant cytokines. Both cytokines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in the lower respiratory tract in IPF and asbestosis.
authors: Department of Medicine, Bellevue Hospital Center, New York University Medical Center, New York 10016.
authors: Y
authors: Y
authors: Zhang
authors: T C
authors: TC
authors: Lee
authors: B
authors: B
authors: Guillemin
authors: M C
authors: MC
authors: Yu
authors: W N
authors: WN
authors: Rom
mesh_terms: D000328:Adult; D001195:Asbestosis / Q000209:etiology / Q000378:metabolism*; D003094:Collagen / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D005353:Fibronectins; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen