title: Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant lipids on this effect.
abstract: Surfactant protein A (SP-A) plays a role in host defense and inflammation in the lung. In the present study, we investigated the hypothesis that SP-A is involved in bleomycin-induced pulmonary fibrosis. We studied the effects of human SP-A on bleomycin-induced cytokine production and mRNA expression in THP-1 macrophage-like cells and obtained the following results. 1) Bleomycin-treated THP-1 cells increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, and IL-1beta production in dose- and time-dependent patterns, as we have observed with SP-A. TNF-alpha levels were unaffected by treatment with cytosine arabinoside. 2) The combined bleomycin-SP-A effect on cytokine production is additive by RNase protection assay and synergistic by enzyme-linked immunosorbent assay. 3) Although the bleomycin effect on cytokine production was not significantly affected by the presence of surfactant lipid, the additive and synergistic effect of SP-A-bleomycin on cytokine production was significantly reduced. We speculate that the elevated cytokine levels resulting from the bleomycin-SP-A synergism are responsible for bleomycin-induced pulmonary fibrosis and that surfactant lipids can help ameliorate pulmonary complications observed during bleomycin chemotherapy.
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: Weixiong
authors.initials: W
authors.lastname: Huang
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
authors.forename: David S
authors.initials: DS
authors.lastname: Phelps
authors.forename: Hamid
authors.initials: H
authors.lastname: Al-Mondhiry
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001688:Biological Products; D001761:Bleomycin / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011510:Proteolipids / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012260:Ribonucleases; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000903:Antibiotics, Antineoplastic; D001688:Biological Products; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D012260:Ribonucleases; C117342:calfactant