| 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 | Weixiong Huang, Guirong Wang, David S Phelps, Hamid Al-Mondhiry, Joanna Floros
(Affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033, USA.)
|
| Journal | American journal of physiology. Lung cellular and molecular physiology
(Am J Physiol Lung Cell Mol Physiol)
Vol. 283
Issue 1
Pg. L94-L102
(Jul 2002)
ISSN: 1040-0605 United States |
| PMID | 12060565
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Antibiotics, Antineoplastic
- Biological Products
- Cytokines
- Interleukin-1
- Interleukin-8
- Proteolipids
- Pulmonary Surfactant-Associated Protein A
- Pulmonary Surfactant-Associated Proteins
- Pulmonary Surfactants
- RNA, Messenger
- Tumor Necrosis Factor-alpha
- calfactant
- Bleomycin
- Ribonucleases
|
| Topics |
- Antibiotics, Antineoplastic
(pharmacology)
- Biological Products
- Bleomycin
(pharmacology)
- Cell Line
- Cytokines
(genetics)
- Dose-Response Relationship, Drug
- Drug Synergism
- Enzyme-Linked Immunosorbent Assay
- Gene Expression
(drug effects, immunology)
- Humans
- Interleukin-1
(genetics)
- Interleukin-8
(genetics)
- Macrophages, Alveolar
(cytology, drug effects, immunology)
- Proteolipids
(pharmacology)
- Pulmonary Surfactant-Associated Protein A
- Pulmonary Surfactant-Associated Proteins
- Pulmonary Surfactants
(pharmacology)
- RNA, Messenger
(analysis)
- Ribonucleases
- Tumor Necrosis Factor-alpha
(genetics)
|
