Immunomodulatory Potential of Thymulin–Zn2+ in the Alveolar Epithelium: Amelioration of Endotoxin-Induced Cytokine Release and Partial Amplification of a Cytoprotective IL-10-Sensitive Pathway

TY - JOUR

T1 - Immunomodulatory Potential of Thymulin–Zn2+ in the Alveolar Epithelium

T2 - Amelioration of Endotoxin-Induced Cytokine Release and Partial Amplification of a Cytoprotective IL-10-Sensitive Pathway

AU - Haddad, John J. E.

AU - Land, Stephen C.

AU - Saadé, Nayef E.

AU - Safieh-Garabedian, Bared

PY - 2000/8/2

Y1 - 2000/8/2

N2 - 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-1β (IC50 = 657 ng·ml-1), but showed no inhibitory effect on IL-6 and TNF-α. Zinc, an anti-inflammatory antioxidant, which is required for the biological activity of thymulin, reduced the secretion of IL-1β (IC50 = 62 μM), TNF-α (IC50 = 1000 μM), and, to a lesser extent, IL-6. This cation (100 μM) amplified the effect of thymulin on IL-1β and TNF-α (IC50 < 0.1 ng·ml-1), but not on IL-6. Analysis of whether thymulin is up-regulating a counterpart antiinflammatory 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. (C) 2000 Academic Press.

AB - 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-1β (IC50 = 657 ng·ml-1), but showed no inhibitory effect on IL-6 and TNF-α. Zinc, an anti-inflammatory antioxidant, which is required for the biological activity of thymulin, reduced the secretion of IL-1β (IC50 = 62 μM), TNF-α (IC50 = 1000 μM), and, to a lesser extent, IL-6. This cation (100 μM) amplified the effect of thymulin on IL-1β and TNF-α (IC50 < 0.1 ng·ml-1), but not on IL-6. Analysis of whether thymulin is up-regulating a counterpart antiinflammatory 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. (C) 2000 Academic Press.

KW - Cytokine

KW - Endotoxin

KW - IL-10

KW - Immunomodulation

KW - Thymulin

KW - Zinc

UR - https://www.scopus.com/pages/publications/0034596221

U2 - 10.1006/bbrc.2000.3155

DO - 10.1006/bbrc.2000.3155

M3 - Article

C2 - 10913367

AN - SCOPUS:0034596221

SN - 0006-291X

VL - 274

SP - 500

EP - 505

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -