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  3. Vibrio harveyi infections induce production of proinflammatory cytokines in murine peritoneal macrophages via activation of p38 MAPK and NF-κB pathways, but reversed by PI3K/AKT pathways

Vibrio harveyi infections induce production of proinflammatory cytokines in murine peritoneal macrophages via activation of p38 MAPK and NF-κB pathways, but reversed by PI3K/AKT pathways

  • Dev Comp Immunol. 2022 Feb;127:104292. doi: 10.1016/j.dci.2021.104292.
Guili Yu 1,  Hong Yu 1,  Qiankun Yang 1,  Jinxin Wang 1,  Hui Fan 1,  Gang Liu 1,  Lei Wang 2,  Babatunde Kazeem Bello 3,  Panpan Zhao 4,  Honggang Zhang 5,  Jingquan Dong 6
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, 222005, China.
  • 2 Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, 222005, China; Department of Vascular Surgery, The First People's Hospital of Lianyungang, Lianyungang, 222002, China.
  • 3 Lianyungang Academy of Agricultural Sciences, Lianyungang, 222006, China.
  • 4 Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, 222005, China; Key Laboratory of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, PR China. Electronic address: zhaopp19@mails.jlu.edu.cn.
  • 5 Department of Vascular Surgery, The First People's Hospital of Lianyungang, Lianyungang, 222002, China. Electronic address: doctorzhang3240@gmail.com.
  • 6 Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address: 2018000029@jou.edu.cn.
PMID: 34656643 DOI: 10.1016/j.dci.2021.104292
Abstract

Vibrio harveyi is a zoonotic pathogen that can infect humans through wounds and cause severe inflammatory responses. Previous studies have reported that the Toll like receptors (TLR) mediated MAPK, Akt and NF-κB signaling pathways are involved in innate immune system resistance to pathogen invasion. However, the molecular mechanism of these pathways, as well as their involvement in V. harveyi Infection remains elusive. This study established a V. harveyi Infection model using murine peritoneal macrophages (PMs). Various techniques, including western blotting, ELISA, RT-qPCR, immunofluorescence, inhibition assays, were used to explore the roles of TLRs, MAPK, Akt and NF-κB signaling pathways in V. harveyi-induced inflammatory responses. ELISA assays showed that V. harveyi Infection triggered proinflammatory cytokines secretion in PMs. RT-qPCR and inhibition assays showed that TLR2 participated in V. harveyi Infection and up-regulated the proinflammatory cytokines secretion in murine PMs. Western blotting data showed that the phosphorylation of p38, JNK, Akt, and NF-κB p65 were significantly increased partly mediated by TLR2. In addition, immunofluorescence assays revealed that the NF-κB p65 translocated into nucleus in response to V. harveyi Infection. The secretion of IL-1β, IL-6, IL-12, and TNF-α were considerably reduced when the p38 MAPK and NF-κB signaling pathways were blocked, whereas blocking of Akt significantly increased the expression of IL-1β, IL-6, IL-12, and TNF-α. These findings indicate that V. harveyi Infection induces inflammatory responses in murine PMs via activation of p38 MAPK and NF-κB pathways, which are partly mediated by TLR2, but are inhibited by PI3K/Akt pathways.

Keywords

AKT; NF-κB p65; Vibrio harveyi; p38 MAPK.

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