TY - JOUR
T1 - A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice
AU - Zhang, Fangming
AU - Brenner, Max
AU - Yang, Weng Lang
AU - Wang, Ping
N1 - Funding Information:
Animals. Adult C57BL/6 mice (25–30 g) were purchased from Jackson Laboratories (Bar Harbor, ME). Mice present sex dimorphism in their susceptibility and inflammatory response to sepsis25–28. Therefore, only male mice were included in this study. Mice were housed in temperature controlled rooms with 12-h light cycles, fed a standard mouse diet, and allowed to acclimate for one week before experimentation. All experiments involving live animals were carried out in agreement with the National Institutes of Health guidelines for the use of experimental animals and were reviewed and approved by the Institutional Animal Care and Use Committee at the Feinstein Institute for Medical Research.
Funding Information:
Ethics approval. All experiments involving live animals were carried out in accordance with the National Institutes of Health guidelines for the use of experimental animals and were reviewed and approved by the Institutional Animal Care and Use Committee at the Feinstein Institute for Medical Research.
Funding Information:
We thank Xiaoling Qiang and Jian Hua Li for their assistance in providing recombinant murine CIRP for this study. We also thank Xiaoling Qiang for conducting the in vitro C23 studies. This study was supported by NIH grants R01 GM053008 (P.W.) and R35 GM118337 (P.W.).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Cold-inducible RNA-binding protein (CIRP) is a novel sepsis inflammatory mediator and C23 is a putative CIRP competitive inhibitor. Therefore, we hypothesized that C23 can ameliorate sepsis-associated injury to the lungs and kidneys. First, we confirmed that C23 dose-dependently inhibited TNF-α release, IκBα degradation, and NF-κB nuclear translocation in macrophages stimulated with CIRP. Next, we observed that male C57BL/6 mice treated with C23 (8 mg/kg BW) at 2 h after cecal ligation and puncture (CLP) had lower serum levels of LDH, ALT, IL-6, TNF-α, and IL-1β (reduced by ≥39%) at 20 h after CLP compared with mice treated with vehicle. C23-treated mice also had improved lung histology, less TUNEL-positive cells, lower serum levels of creatinine (34%) and BUN (26%), and lower kidney expression of NGAL (50%) and KIM-1 (86%). C23-treated mice also had reduced lung and kidney levels of IL-6, TNF-α, and IL-1β. E-selectin and ICAM-1 mRNA was significantly lower in C23-treated mice. The 10-day survival after CLP of vehicle-treated mice was 55%, while that of C23-treated mice was 85%. In summary, C23 decreased systemic, lung, and kidney injury and inflammation, and improved the survival rate after CLP, suggesting that it may be developed as a new treatment for sepsis.
AB - Cold-inducible RNA-binding protein (CIRP) is a novel sepsis inflammatory mediator and C23 is a putative CIRP competitive inhibitor. Therefore, we hypothesized that C23 can ameliorate sepsis-associated injury to the lungs and kidneys. First, we confirmed that C23 dose-dependently inhibited TNF-α release, IκBα degradation, and NF-κB nuclear translocation in macrophages stimulated with CIRP. Next, we observed that male C57BL/6 mice treated with C23 (8 mg/kg BW) at 2 h after cecal ligation and puncture (CLP) had lower serum levels of LDH, ALT, IL-6, TNF-α, and IL-1β (reduced by ≥39%) at 20 h after CLP compared with mice treated with vehicle. C23-treated mice also had improved lung histology, less TUNEL-positive cells, lower serum levels of creatinine (34%) and BUN (26%), and lower kidney expression of NGAL (50%) and KIM-1 (86%). C23-treated mice also had reduced lung and kidney levels of IL-6, TNF-α, and IL-1β. E-selectin and ICAM-1 mRNA was significantly lower in C23-treated mice. The 10-day survival after CLP of vehicle-treated mice was 55%, while that of C23-treated mice was 85%. In summary, C23 decreased systemic, lung, and kidney injury and inflammation, and improved the survival rate after CLP, suggesting that it may be developed as a new treatment for sepsis.
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U2 - 10.1038/s41598-017-13139-z
DO - 10.1038/s41598-017-13139-z
M3 - Article
C2 - 29434211
AN - SCOPUS:85041948975
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 3052
ER -