Role Of IL-33 In Inflammation Research Articles

IL-33 deficiency inhibits Toxoplasma gondii infection by promoting NLRP3 inflammasome.

NLRP3 inflammasome-mediated inflammatory responses play pivotal functions in innate immunity. However, its homeostatic regulation still needs to be better understood. Here we explore the effect and potential mechanism of IL-33 on NLRP3 inflammasome upon Toxoplasma gondii infection through a series of molecular biology and immunological experiments, including western blot, qRT-PCR, and ELISA. We demonstrated that T. gondii infection induces the expression of IL-33, and IL-33-deficient (IL-33-/-) mice exhibit longer survival time than wild-type (WT) mice upon T. gondii infection. IL-33 deficiency promotes the expression of NLRP3 and ASC and the secretion of IL-1β, while exogenous IL-33 inhibits NLRP3 inflammasome. Furthermore, T. gondii infection results in the M2 polarization of macrophages, exacerbated by exogenous IL-33, which also promotes the proliferation of T. gondii. These findings showed that IL-33 deficiency attenuates T. gondii infection by promoting NLRP3 inflammasome, advancing the understanding of the role of IL-33 in inflammation.

IL-33 and its decoy sST2 in patients with Alzheimer\u2019s disease and mild cognitive impairment

BackgroundInterleukin-33 is a cytokine endowed with pro- and anti-inflammatory properties that plays a still poorly defined role in the pathogenesis of a number of central nervous system (CNS) conditions including Alzheimer’s disease (AD). We analyzed this cytokine and its decoy receptor sST2 in Alzheimer’s disease (AD) and mild cognitive impairment (MCI).MethodIL-33 and sST2 were analyzed in serum and CSF of AD and MCI patients, comparing the results to those obtained in age-matched healthy controls (HC). Because of the ambiguous role of IL-33 in inflammation, the concentration of both inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was analyzed as well in serum and cerebrospinal fluid (CSF) of the same individuals. Finally, the effect of IL-33 on in vitro Aβ42-stimulated monocytes of AD, MCI, and HC individuals was examined.ResultsAs compared to HC, (1) IL-33 was significantly decreased in serum and CSF of AD and MCI, (2) sST2 was increased in serum of AD and MCI but was undetectable in CSF, (3) serum and CSF IL-1β concentration was significantly increased and that of IL-10 was reduced in AD and MCI, whereas no differences were observed in IL-6. In vitro addition of IL-33 to LPS+Aβ 42-stimulated monocytes downregulated IL-1β generation in MCI and HC, but not in AD, and stimulated IL-10 production in HC alone. IL-33 addition also resulted in a significant reduction of NF-kB nuclear translocation in LPS+Aβ42-stimulated monocytes of HC alone.ConclusionsThese data support the hypothesis that IL-33 plays a complex anti-inflammatory role that is lost in AD- and MCI-associated neuroinflammation; results herein also suggest a possible use of IL-33 as a novel therapeutic approach in AD and MCI.

THU0228 Serum IL-33 level in behçet’s disease and rheumatoid arthritis

BackgroundBehçet’s disease (BD) is a systemic vasculitis characterized by a triad of recurrent oral and genital ulcers and uveitis. Although the pathogenesis of BD remains uncertain, immunological abnormalities is mediated...

Role of IL-33 in inflammation and disease

Interleukin (IL)-33 is a new member of the IL-1 superfamily of cytokines that is expressed by mainly stromal cells, such as epithelial and endothelial cells, and its expression is upregulated following pro-inflammatory stimulation. IL-33 can function both as a traditional cytokine and as a nuclear factor regulating gene transcription. It is thought to function as an 'alarmin' released following cell necrosis to alerting the immune system to tissue damage or stress. It mediates its biological effects via interaction with the receptors ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP), both of which are widely expressed, particularly by innate immune cells and T helper 2 (Th2) cells. IL-33 strongly induces Th2 cytokine production from these cells and can promote the pathogenesis of Th2-related disease such as asthma, atopic dermatitis and anaphylaxis. However, IL-33 has shown various protective effects in cardiovascular diseases such as atherosclerosis, obesity, type 2 diabetes and cardiac remodeling. Thus, the effects of IL-33 are either pro- or anti-inflammatory depending on the disease and the model. In this review the role of IL-33 in the inflammation of several disease pathologies will be discussed, with particular emphasis on recent advances.