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Mediators Inflamm. 2018 Jul 26;2018:9629537. doi: 10.1155/2018/9629537. eCollection 2018.

TRAIL and Ceruloplasmin Inverse Correlation as a Representative Crosstalk between Inflammation and Oxidative Stress.

Author information

1
Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.
2
Department of Medical Science, University of Ferrara, Ferrara, Italy.
3
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
4
Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
5
Department of Animal Sciences, Plants for Human Health Institute, NC State University, NC Research Campus, Kannapolis, NC, USA.

Abstract

Objective:

"Oxinflammation" is a recently coined term that defines the deleterious crosstalk between inflammatory and redox systemic processes, which underlie several diseases. Oxinflammation could be latently responsible for the predisposition of certain healthy individuals to disease development. The oxinflammatory pathway has been recently suggested to play a crucial role in regulating the activity of TNF-related apoptosis-inducing ligand (TRAIL), a TNF superfamily member that can mediate multiple signals in physiological and pathological processes. Therefore, we investigated the associations between TRAIL and key players of vascular redox homeostasis.

Methods:

We measured circulating TRAIL levels relative to praoxonas-1, lipoprotein phospholipase-A2, and ceruloplasmin levels in a cohort of healthy subjects (n = 209).

Results:

Multivariate analysis revealed that ceruloplasmin levels were significantly inversely associated with TRAIL levels (r = -0.431, p < 0.001). The observed association retained statistical significance after adjustment for additional confounding factors. After stratification for high-sensitivity C-reactive protein levels, the inverse association between TRAIL and ceruloplasmin levels remained strong and significant (r = -0.508, p < 0.001, R2 = 0.260) only in the presence of inflammation, confirming the role of inflammation as emerged in in vitro experiments where recombinant TRAIL decreased ceruloplasmin expression levels in TNF-treated PBMC cultures.

Conclusion:

The results indicated that in an inflammatory milieu, TRAIL downregulates ceruloplasmin expression, highlighting a signaling axis involving TRAIL and ceruloplasmin that are linked via inflammation and providing important insights with potential clinical implications.

PMID:
30147446
PMCID:
PMC6083483
DOI:
10.1155/2018/9629537
[Indexed for MEDLINE]
Free PMC Article

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