Lipopolysaccharide induces and activates the Nalp3 inflammasome in the liver

Michal Ganz, Timea Csak, Bharath Nath, Gyongyi Szabo

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

AIM: To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide (LPS)-induced stimulation in the liver. METHODS: Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5 μg/g bodyweight LPS and sacrificed 2, 4, 6, 18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase (ALT) levels. To determine if LPS stimulation in the liver led to activation of the inflammasome, real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome. Enzyme-linked immunosorbent assays were used to determine the protein expression levels of several downstream targets of the Nalp3 inflammasome, including caspase-1 and two cytokine targets of caspase-1, interleukin (IL)-1β and IL-18. RESULTS: We found that LPS injection resulted in liver damage as indicated by elevated ALT levels. This was associated with a significant increase in both mRNA and protein levels of the proinflammatory cytokine tumor necrosis factor (TNF)-α in the liver, as well as increased levels of TNFs in serum. We showed that LPS stimulation led to upregulation of mRNA levels in the liver for all the receptor components of the inflammasome, including Nalp3, Nalp1, pannexin-1 and the adaptor molecule apoptosis-associated specklike, caspase recruitment domain-domain containing protein. We also found increased levels of mRNA and protein for caspase-1, a downstream target of the inflammasome. In addition, LPS challenge led to increased levels of both mRNA and protein in the liver for two cytokine targets of caspase-1, IL-1β and IL-18. Interestingly, substantial baseline expression of pre-IL- 1β and pre-IL-18 was found in the liver. Inflammasome and caspase-1 activation was indicated by the significant increase in the active forms of IL-1β and IL-18 after LPS stimulation. CONCLUSION: Our results show that the Nalp3 inflammasome is upregulated and activated in the liver in response to LPS stimulation.

Original languageEnglish
Pages (from-to)4772-4778
Number of pages7
JournalWorld journal of gastroenterology
Volume17
Issue number43
DOIs
Publication statusPublished - Nov 21 2011

Keywords

  • Caspase-1
  • Endotoxin
  • Interleukin-18
  • Interleukin-1β
  • Nod-like receptor

ASJC Scopus subject areas

  • Gastroenterology

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