DhHP-6 alleviates inflammation and reduces vascular permeability by eliminating reactive oxygen species

Abstract

Inflammation is a defensive immune response to external stimuli. However, uncontrolled inflammation may cause potential damage to the host. Therefore, timely control of uncontrolled inflammation is particularly important. Previous studies have found that small molecules with antioxidant activity, such as peroxidase mimic enzymes, can inhibit the development of inflammation. DhHP-6 is a new peptide mimic of peroxidase previously designed by our laboratory. Here, we explored its anti-inflammatory activity in vitro and in vivo. Our results showed that treatment with DhHP-6 significantly reduced the production of reactive oxygen species (ROS), NO, IL-6, and TNF-α in RAW264.7 cells induced by lipopolysaccharides (LPS); in addition, it also blocked the phosphorylation of extracellularly regulated kinase 1 and 2 (ERK1/2) and ribosomal s6 kinase 1 (RSK1), thereby blocking the phosphorylation and degradation of IκBα, and inhibiting the nuclear translocation of p65. Interestingly, treatment with DhHP-6 blocked the phosphorylation of ERK1/2 and myosin light chain kinase (MLCK) in HUVECs induced by LPS. Finally, we found that DhHP-6 treatment significantly reduced the infiltration of immune cells in balloon model rats. Therefore, we believe that DhHP-6 is a potent inhibitor of inflammation.

Keywords:

• DhHP-6
• inflammation
• NF-κB
• ROS
• vascular permeability

Acknowledgments

We thank the National Natural Science Foundation of China, and the Science and Technology Development Program of Jilin Province, China.

Author contributions

Methodology, Fanwei Meng; Resources, Fanwei Meng and Junfeng Ke; Software, Feng Guo; Visualization, Fanwei Meng and Junfeng Ke; Writing – original draft, Fanwei Meng and Junfeng Ke; Writing – review & editing, Liping Wang.

Disclosure statement

The authors declare no conflict of interest.

Institutional review board statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Laboratory Animal Center of the School of Life Sciences, Jilin University (protocol code: 20210417).

Additional information

Funding

This work was supported by the Science and Technology Development Program of Jilin Province, China (No.20200404114YY, No. 20200301029RQ).