title: Pentoxifylline inhibits ICAM-1 expression and chemokine production induced by proinflammatory cytokines in human pulmonary epithelial cells.
abstract: Airway epithelium participates in inflammatory reactions by producing chemokines and expressing cell-surface adhesion molecules which aid in the selective recruitment of effector cells. Previous studies showed that proinflammatory cytokines, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF alpha), induce surface expression of intercellular adhesion molecule 1 (ICAM-1) and the production of the chemokines interleukin 8 (IL-8) and monocyte chemoattractant protein (MCP-1) on pulmonary epithelial cell lines in vitro. In this study, the dose response of four cytokines, IL-1alpha, IL-1beta, TNF alpha and TNF beta, in inducing ICAM-1 expression and production of IL-8 and MCP-1 on pulmonary A549 epithelial cells was examined. Both IL-1alpha and IL-1beta induced ICAM-1 expression and IL-8 and MCP-1 production at lower doses than TNF alpha or TNF beta. Pentoxifylline, an anti-inflammatory agent used to treat vascular diseases, was tested for its ability to inhibit the activation of airway epithelial cells by these cytokines. Pentoxifylline completely inhibited the surface expression of ICAM-1 and the production of IL-8 and MCP-1 by cytokine-activated epithelial cells. As elevated levels of chemokines are often present in bronchial lavage fluids of patients suffering from various acute respiratory diseases, pentoxifylline may be useful for preventing the rapid development of immune reactions leading to lung injury.
authors.affiliation: Department of Immunology and Molecular Biology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: T
authors.initials: T
authors.lastname: Krakauer
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D010431:Pentoxifylline