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 journalArticle

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 1 2018

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T-cells
Macrophages
Creatinine
Down-Regulation
Tumor Necrosis Factor-alpha
T-Lymphocytes
Cell Line
Cells
Lipopolysaccharides
Chemical activation
Waste Products
Inflammation
Creatine
Cell culture
Anti-Inflammatory Agents
Adenosine Triphosphate
Cytokines
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

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

Cite this

Riesberg, L. A., McDonald, T. L., Wang, Y., Chen, X-M., Holzmer, S. W., Tracy, S. M., & Drescher, K. M. (2018). Creatinine downregulates TNF-α in macrophage and T cell lines. Cytokine, 110, 29-38. https://doi.org/10.1016/j.cyto.2018.04.021

Creatinine downregulates TNF-α in macrophage and T cell lines. / Riesberg, Lisa A.; McDonald, Thomas L.; Wang, Yang; Chen, Xian-Ming; Holzmer, Stephanie W.; Tracy, Steven M.; Drescher, Kristen M.

In: Cytokine, Vol. 110, 01.10.2018, p. 29-38.

Research output: Contribution to journalArticle

Riesberg, LA, McDonald, TL, Wang, Y, Chen, X-M, Holzmer, SW, Tracy, SM & Drescher, KM 2018, 'Creatinine downregulates TNF-α in macrophage and T cell lines', Cytokine, vol. 110, pp. 29-38. https://doi.org/10.1016/j.cyto.2018.04.021
Riesberg LA, McDonald TL, Wang Y, Chen X-M, Holzmer SW, Tracy SM et al. Creatinine downregulates TNF-α in macrophage and T cell lines. Cytokine. 2018 Oct 1;110:29-38. https://doi.org/10.1016/j.cyto.2018.04.021
Riesberg, Lisa A. ; McDonald, Thomas L. ; Wang, Yang ; Chen, Xian-Ming ; Holzmer, Stephanie W. ; Tracy, Steven M. ; Drescher, Kristen M. / Creatinine downregulates TNF-α in macrophage and T cell lines. In: Cytokine. 2018 ; Vol. 110. pp. 29-38.
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