Dimethylnitrosamine (DMN)-induced IL-1β, TNF-α, and IL-6 inflammatory cytokine expression

L. B. Schook, J. F. Lockwood, S. D. Yang, M. J. Myers

Research output: Contribution to journalArticlepeer-review

Abstract

Altered immune functions have been demonstrated in mice following exposure to dimethylnitrosamine (DMN). In particular, changes in cell-mediated immune responses resulted from chronic DMN exposure in vivo. Since cytokines are potent immunoregulatory peptides, experiments were performed to determine whether DMN exposure results in the induction of serum-borne inflammatory cytokines. Animals were exposed to either vehicle (PBS) or DMN (5.0 mg/kg) every 24 hr for 14 days. Serum and liver samples were obtained from individual mice at 0, 1, 2, 3, 6, 12, and 24 hr following the first exposure, with additional samples collected every 24 hr preceeding the daily DMN exposure. Sera were then analyzed for IL-1β, IL-3, IL-6, CSF-1, GM-CSF, and TNF-α activities using either biological or immunological assays. In addition, liver total cellular RNA was probed for the induction of IL-1β transcripts using the solution hybridization/RNase protection assay. IL-1β, IL-6, and TNF-α serum activities were observed within 2 hr of DMN exposure and returned to vehicle control levels by 3 days even though DMN exposure was maintained. Chronic expression of cytokine activity (after 72 hr) was only observed for GM-CSF. A rapid induction of IL-1β transcripts (within 1 hr) in both vehicle and DMN-treated animals was observed by solution hybridization. However, by 3 hr postexposure, transcript levels decreased in the vehicle-treated animals while remaining elevated in the DMN-treated animals for 6 hr. These results demonstrated that DMN exposure in vivo induced: (1) the expression of serum-borne cytokine activities, and (2) IL-1β transcription in liver tissue.

Original languageEnglish (US)
Pages (from-to)110-116
Number of pages7
JournalToxicology and Applied Pharmacology
Volume116
Issue number1
DOIs
StatePublished - Sep 1992

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'Dimethylnitrosamine (DMN)-induced IL-1β, TNF-α, and IL-6 inflammatory cytokine expression'. Together they form a unique fingerprint.

Cite this