1. Academic Validation
  2. Cl-amidine attenuates lipopolysaccharide-induced mouse mastitis by inhibiting NF-κB, MAPK, NLRP3 signaling pathway and neutrophils extracellular traps release

Cl-amidine attenuates lipopolysaccharide-induced mouse mastitis by inhibiting NF-κB, MAPK, NLRP3 signaling pathway and neutrophils extracellular traps release

  • Microb Pathog. 2020 Dec;149:104530. doi: 10.1016/j.micpath.2020.104530.
Chaoqun Wang 1 Jingjing Wang 2 Xiao Liu 2 Zhen Han 2 Aimin Jiang 2 Zhengkai Wei 3 Zhengtao Yang 4
Affiliations

Affiliations

  • 1 College of Life Sciences and Engineering, Foshan University, Foshan, 528225, Guangdong Province, PR China; Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin province, PR China.
  • 2 Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin province, PR China.
  • 3 College of Life Sciences and Engineering, Foshan University, Foshan, 528225, Guangdong Province, PR China.
  • 4 College of Life Sciences and Engineering, Foshan University, Foshan, 528225, Guangdong Province, PR China. Electronic address: yangzt@fosu.edu.cn.
Abstract

Cl-amidine, a peptidylarginine deiminase inhibitor, has been shown to ameliorate the disease course and clinical manifestation in variety of disease models. Due to the beneficial effects of Cl-amidine, it has been becoming the hottest compound for the study in inflammatory diseases. However, the anti-inflammatory activity of Cl-amidine in lipopolysaccharide (LPS)-induced mouse mastitis remains unclear. In this study, we investigated the effects of Cl-amidine on LPS-induced mastitis mouse model. The mouse mastitis model was established by injection of LPS through the canals of the mammary gland. Cl-amidine was administered intraperitoneally 1 h before LPS treatment. The results showed that Cl-amidine significantly attenuated the damage of the mammary gland, which suppressed the activity of myeloperoxidase (MPO). The Real-Time PCR results indicated that Cl-amidine inhibited the production of TNF-α, IL-1β and IL-6 in LPS-induced mouse mastitis. Moreover, the western blot results indicated that Cl-amidine decreased the phosphorylation of IκB, p65, p38, ERK and the expression of NLRP3 in LPS-induced mouse mastitis. Furthermore, the neutrophils extracellular traps (NETs) were determined by Quant-iT picogreen dsDNA assay kit®, which suggested that Cl-amidine significantly inhibited the NETs in mouse serum. This study demonstrated that Cl-amidine decreased the pathological injury in LPS-induced mouse mastitis by inhibiting NF-κB, MAPK, NLRP3 signaling pathway and NETs release, which provides a potential candidate for the treatment of mastitis.

Keywords

Cl-amidine; Lipopolysaccharide; Mastitis.

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