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.
N1 - Funding Information:
This work was supported by funding from LB692-State of Nebraska and Vireo Systems . This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program (1 C06 RR17417-01) from the National Center for Research Resources, National Institutes of Health (NIH) . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
Funding Information:
The Integrated Biological Imaging Facility at Creighton University, Omaha, NE is supported by the Creighton University School of Medicine and grants GM103427 and GM110768 from the National Institute of General Medical Science (NIGMS), a component of the NIH. The facility was constructed with support from grants from the National Center for Research Resources ( RR016469 ) and the NIGMS ( GM103427 ). This investigation is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or NIH.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/10
Y1 - 2018/10
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.
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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 -