Chemerin alleviates acute pancreatitis in the rat thorough modulation of NF-κB signal

Pancreatology. 2019 Apr;19(3):401-408. doi: 10.1016/j.pan.2019.02.005. Epub 2019 Feb 11.

Abstract

Objective: Chemerin, an adipokine, works as the chemoattractant for the immune cells. The role of chemerin in the inflammatory reaction is controversial. Chemerin has been shown to aggravate the inflammatory response, but other studies demonstrated its anti-inflammatory influence. This study assessed the effects of chemerin on acute pancreatitis (AP) in vivo and in vitro.

Methods: For in vivo experiments male Wistar rats were used. For in vitro study rat pancreatic AR42J cells were employed. Chemerin (1, 5 or 10 μg/kg) was given to the rats prior to the induction of AP by subcutaneous caerulein infusion (25 μg/kg). For in vitro studies cells were subjected to caerulein (10 nM) with or without chemerin (100 nM). Serum amylase activity was measured by enzymatic method, serum TNFα concentration - by ELISA kit. Western-blot was used to examine cellular proteins.

Results: AP was confirmed by histological examination. Chemerin given to AP rats decreased histological manifestations of AP, reduced serum amylase activity and TNFα concentration. In AR42J cells subjected to caerulein with addition of chemerin signal for TNFα was reduced comparing to the cultures treated with caerulein alone. Analysis of the dynamics of nuclear translocation for p50, p65 and Bcl-3 points out to NF-κB attenuation as a mechanism of observed anti-inflammatory action of chemerin.

Conclusion: Chemerin significantly alleviated severity of AP in the rat, this is possibly due to the inhibition of pro-inflammatory signaling in the pancreatic cells.

Keywords: Acute pancreatitis; Chemerin; Inflammation; NF-kB; TNF α.

MeSH terms

  • Animals
  • Cell Line
  • Ceruletide / toxicity
  • Chemokines / administration & dosage
  • Chemokines / therapeutic use*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Intercellular Signaling Peptides and Proteins / administration & dosage
  • Intercellular Signaling Peptides and Proteins / therapeutic use*
  • Male
  • NF-kappa B / metabolism*
  • Pancreas / cytology
  • Pancreatitis / chemically induced*
  • Pancreatitis / drug therapy
  • Rats
  • Rats, Wistar

Substances

  • Chemokines
  • Intercellular Signaling Peptides and Proteins
  • NF-kappa B
  • Rarres2 protein, rat
  • Ceruletide