Ulinastatin suppresses lipopolysaccharide induced neuro-inflammation through the downregulation of nuclear factor-κB in SD rat hippocampal astrocyte

Journal Article · Fri Mar 20 04:00:00 EDT 2015 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.01.155· OSTI ID:22458536

Li, Yuting; Zhao, Lei; Fu, Huiqun ^[1]; Wu, Yan ^[2]; Wang, Tianlong ^[1]

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1. Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China)
2. Department of Anatomy, Capital Medical University, 100069 Beijing (China)

Astrocyte activation plays a pivotal role in neuroinflammation, which contributes to neuronal damage, so the inhibition of astrocyte activation may alleviate the progression of neurodegeneration. Recent studies have proved that urinary trypsin inhibitor ulinastatin could inhibit NF-kB activation. In our study, the inhibitory effects of ulinastatin on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-reduced primary astrocyte. Our results showed that ulinastatin significantly inhibited LPS-induced astrogliosis, which is measured by MTT and BrdU. Ulinastatin decreased the production of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, it significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and also increased the protein levels of IκB-α binded to NF-κB, which blocked NF-κB translocation to the nucleus and prevented its activity. Our results suggest that ulinastatin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The study provides direct evidence of potential therapy methods of ulinastatin for the treatment of neuroinflammatory diseases. - Highlights: • The anti-inflammatory effect of UTI on hippocampal astrocyte. • UTI showed protective effect on neuroinflammation by the downregulation of NF-κB. • UTI led to expression of cytokines decreased in concentration and time dependence.

• OSTI ID: 22458536
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 458; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CONCENTRATION RATIO
DISEASES
INFLAMMATION
INHIBITION
LYMPHOKINES
MESSENGER-RNA
RATS
SIGNALS
THERAPY
TIME DEPENDENCE
TRANSLOCATION
TRYPSIN