Creatinine downregulates TNF-α in macrophage and T cell lines

Lisa A. Riesberg, Thomas L. McDonald, Yang Wang, Xian Ming Chen, Stephanie W. Holzmer, Steven M. Tracy, Kristen M. Drescher

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Creatinine is the breakdown product of creatine, a key participant in the generation of ATP and is traditionally considered to be a biologically inert waste product. Based on our earlier work, we analyzed the effects of creatinine hydrochloride on the expression of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, in a human T cell line, as well as human and mouse macrophage cell lines. Exposing cells to creatinine hydrochloride significantly reduced TNF-α mRNA and protein levels compared to control-treated cultures in all cell lines tested. Lipopolysaccharide (LPS), a potent inducer of inflammation, was employed with in mouse macrophage cell lines to induce high levels of TNF-α in order to determine whether creatinine hydrochloride could reduce preexisting inflammation. Cells treated with LPS and creatinine hydrochloride had significantly reduced TNF-α levels compared to cells treated with LPS alone. As the NF-κB signaling pathway represents a major mechanism of TNF-α generation, nuclear extracts were examined for NF-κB pathway activation. Cells exposed to CRN had significantly lower levels of NF-κB in the nucleus compared to control-treated cells. Together, these results support the hypothesis that CRN can alter anti-inflammatory responses by interfering with the activation of the NF-κB pathway.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalCytokine
Volume110
DOIs
StatePublished - Oct 2018

Keywords

  • Creatine
  • Creatinine
  • Creatinine hydrochloride
  • Immunomodulation
  • Macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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