[The relationship between NLRP3 inflammsomes expression and liver damage after allogeneic hematopoietic stem cell transplantation in mice model]

Zhonghua Xue Ye Xue Za Zhi. 2014 Aug;35(8):684-8. doi: 10.3760/cma.j.issn.0253-2727.2014.08.003.
[Article in Chinese]

Abstract

Objective: To explore the function of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammsomes in liver damage after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: The study presented a murine (BALB/c-based) model of allo-HSCT. Chimera rate was measured by flow cytometry. The hematoxylin-eosin, Masson's trichrome, immunohistochemistry staining were used to observe the pathology changes in liver, then measured the degree of liver damage. Inflammation cells and NLRP3 were measured by Western blot, cytokines IL-1β, IL-18 and NLRP3 related genes were tested with real-time quantitative polymerase chain reaction (q-PCR).

Results: Hematopoietic stem cells had been successfully transplanted, the chimera rate was geater than 97% on the 10th day. Liver damage occurred after allo-HSCT and suffered infiltration of inflammation cells, which reached the peak on day 15, then moved to moderate; the cytokines IL-1β, IL-18 had the similar trend with liver injury, and reached the highest level on day 15, their mRNA expressions increased by (1.19 ± 0.40) fold and (1.64 ± 0.76) fold, respectively; Meanwhile, caspase-1 had the similar trend, its mRNA expression increased by (3.51 ± 0.46) fold on day 15; the inflammasomes NLRP1, NLRP3, NLRC4 and NLRP5 expressed in liver on day 15 of post-allo-HSCT, and NLRP3 inflammasome expressed highest among them. The mRNA and protein level of NLRP3 inflammasomes were kept with the serious degree of the liver damage, its mRNA expression increased by (2.91 ± 0.41) fold on day 15.

Conclusion: NLRP3 inflammsome expressed in liver injury during allo-HSCT in mice, and may be one of the important factors contributed to liver injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Inflammasomes / metabolism*
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Postoperative Period

Substances

  • Carrier Proteins
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human