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 language | English (US) |
|---|---|
| Pages (from-to) | 29-38 |
| Number of pages | 10 |
| Journal | Cytokine |
| Volume | 110 |
| DOIs | |
| State | Published - Oct 1 2018 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Biochemistry
- Hematology
- Molecular Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Creatinine downregulates TNF-α in macrophage and T cell lines
AU - Riesberg, Lisa A.
AU - McDonald, Thomas L.
AU - Wang, Yang
AU - Chen, Xian-Ming
AU - Holzmer, Stephanie W.
AU - Tracy, Steven M.
AU - Drescher, Kristen M.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046168695&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046168695&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2018.04.021
DO - 10.1016/j.cyto.2018.04.021
M3 - Article
C2 - 29698843
AN - SCOPUS:85046168695
VL - 110
SP - 29
EP - 38
JO - Cytokine
JF - Cytokine
SN - 1043-4666
ER -