Elevated caspase‑1 activity and IL‑1β expression are associated with the IPAF inflammasome in an experimental model of allergy

Mol Med Rep. 2016 Apr;13(4):3356-62. doi: 10.3892/mmr.2016.4934. Epub 2016 Feb 23.

Abstract

Previous studies have indicated that interleukin (IL)‑1β has an important role in the development of allergic diseases. Therefore, the present study aimed to investigate the upstream pathway underlying IL‑1β production in an experimental model of allergy. BALB/c mice (female, 6‑8 weeks old) were sensitized to recombinant (r)Che a 2 by intraperitoneal injection of rChe a 2 adsorbed onto an alum gel suspension on days 0, 7, 14 and 21. In the control group, mice received an injection of 20 mM phosphate‑buffered saline absorbed onto alum via the same route. The allergic status of the mice was confirmed serologically by measuring allergen‑specific immunoglobulin (Ig)E levels. The protein expression levels of IL‑1β and the mRNA expression levels of inflammasome compartments were measured by enzyme‑linked immunosorbent assay and semi‑quantitative reverse transcription polymerase chain reaction, respectively. In addition, caspase‑1 activity was determined by fluorometric assay. Sensitized mice exhibited significantly increased levels of specific IgE (P<0.05). IL‑1β production and caspase‑1 activity were significantly higher in the sensitized mice compared with the control group. In addition, no significant differences were observed between the control and sensitized mice in the expression of genes associated with the inflammasome, including NLR family, pyrin domain containing 3; apoptosis‑associated speck‑like protein; and NLR family, apoptosis inhibitory protein 5. However, IL‑1β converting enzyme protease‑activating factor (IPAF) expression was significantly increased in sensitized mice compared with in the control group (P<0.05). These data indicate that caspase‑1 activation and IL‑1β expression are associated with the IPAF inflammasome. Therefore, based on this association, the IPAF inflammasome may be considered for IL‑1β production in the experimental model of allergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Caspase 1 / metabolism*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorometry
  • Hypersensitivity / immunology
  • Hypersensitivity / metabolism
  • Hypersensitivity / pathology*
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Hypoxanthine Phosphoribosyltransferase / metabolism
  • Immunoglobulin E / metabolism
  • Inflammasomes / metabolism*
  • Interleukin-1beta / analysis
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Neuronal Apoptosis-Inhibitory Protein / genetics
  • Neuronal Apoptosis-Inhibitory Protein / metabolism
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Ipaf protein, mouse
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Naip5 protein, mouse
  • Neuronal Apoptosis-Inhibitory Protein
  • Nlrp3 protein, mouse
  • RNA, Messenger
  • Immunoglobulin E
  • Hypoxanthine Phosphoribosyltransferase
  • Caspase 1