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.
IntroductionAn allergic response is characterized by an exaggerated immune reaction to certain antigens, including harmless environmental antigens from various sources, such as food and pollen. Approximately 25% of the population in developed countries suffers from immunoglobulin (Ig)E-mediated type I allergy (1,2). Interleukin (IL)-1β has been identified as an important cytokine, which has a key role in the pathophysiology of allergic disorders (3). Furthermore, IL-1β has an essential role in the immune response to infectious agents (4).IL-1β can be produced by immune cells, including blood monocytes, tissue macrophages and dendritic cells (5). IL-1β secretion is a two-step process: Firstly, interaction of Toll-like receptors (TLRs) with their ligands leads to an upregulation of pro-IL-1β gene transcription via nuclear factor-κB (6). Secondly, caspase-1 activation results in the conversion of the immature pro-IL-1β into mature IL-1β. It is well-established that caspase-1 activity is regulated by a cytosolic multi-protein complex known as the inflammasome (7). The inflammasome consists of a nucleotide-binding domain like receptor (NLR), o...