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Immunomodulatory potential of thymulin-Zn(2+) in the alveolar epithelium: amelioration of endotoxin-induced cytokine release and partial amplification of a cytoprotective IL-10-sensitive pathway.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2000 Aug 02; Vol. 274 (2), pp. 500-5. - Publication Year :
- 2000
-
Abstract
- The immunomodulatory potential of thymulin in the perinatal epithelium is not well characterized. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the exhibition of an anti-inflammatory activity of this peptide hormone. Thymulin selectively ameliorated, in a dose-dependent manner, the endotoxin-induced release of IL-1 beta (IC(50) = 657 ng. ml(-1)), but showed no inhibitory effect on IL-6 and TNF-alpha. Zinc, an anti-inflammatory antioxidant, which is required for the biological activity of thymulin, reduced the secretion of IL-1 beta (IC(50) = 62 microM), TNF-alpha (IC(50) = 1000 microM), and, to a lesser extent, IL-6. This cation (100 microM) amplified the effect of thymulin on IL-1 beta and TNF-alpha (IC(50) < 0.1 ng. ml(-1)), but not on IL-6. Analysis of whether thymulin is up-regulating a counterpart anti-inflammatory signaling loop revealed the involvement of an IL-10-sensitive pathway. These results indicate that thymulin acts as a novel dual immunoregulator by enhancing an anti-inflammatory cytoprotective response and depressing an inflammatory signal, an effect synergistically amplified, in part, by cationic zinc.<br /> (Copyright 2000 Academic Press.)
- Subjects :
- Adjuvants, Immunologic pharmacology
Animals
Anti-Inflammatory Agents metabolism
Anti-Inflammatory Agents pharmacology
Cytokines biosynthesis
Cytoprotection drug effects
Cytoprotection immunology
Dose-Response Relationship, Drug
Down-Regulation drug effects
Drug Synergism
Endotoxins pharmacology
Epithelial Cells drug effects
Epithelial Cells metabolism
Interleukin-1 biosynthesis
Interleukin-6 biosynthesis
Pulmonary Alveoli cytology
Pulmonary Alveoli drug effects
Rats
Signal Transduction drug effects
Signal Transduction immunology
Thymic Factor, Circulating pharmacology
Tumor Necrosis Factor-alpha biosynthesis
Up-Regulation drug effects
Zinc pharmacology
Adjuvants, Immunologic metabolism
Cytokines metabolism
Epithelial Cells immunology
Interleukin-10 metabolism
Pulmonary Alveoli immunology
Thymic Factor, Circulating metabolism
Zinc metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 274
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 10913367
- Full Text :
- https://doi.org/10.1006/bbrc.2000.3155