A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut
Abstract
:1. Introduction
2. Biological Characteristics of IL-33
2.1. The IL-33 Release Mechanism
2.2. The Transcriptional Regulatory Role of IL-33 in the Cell Nucleus
2.3. IL-33 Exerts Its Function in Innate Immunity
2.3.1. Double-Edged Sword Effect of IL-33 and ILC2 on Intestinal Epithelium
2.3.2. IL-33 Induces Eosinophil Recruitment
2.4. The Role of IL-33 in Adaptive Immunity
2.4.1. IL-33 Regulates the Proliferation of Treg Cells
2.4.2. IL-33 Induces Th2 Immune Responses
2.5. The “Sentry” Role of IL-33
2.6. The Role of IL-33 in the Gut
3. Classification and Expression of ST2
3.1. ST2L
3.2. sST2
4. Regulation of the IL-33/ST2 Axis
5. IBD Pathogenesis Is Complicated by Cytokines and Multiple Aspects
6. The Role of IL-33 in IBD
6.1. Evidence of the Role of IL-33 in IBD
6.2. Possible Mechanism of Dual Action of IL-33 in IBD
7. IL-33 Is Involved in Parasitic Infections
8. The Role of IL-33 in Gastrointestinal Cancer
9. Therapeutic Drugs and Targets for IL-33-Related Diseases
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
Inflammatory bowel disease | IBD |
ulcerative colitis | UC |
Crohn’s disease | CD |
Interleukin-33 | IL-33 |
Innate lymphoid cell type 2 | ILC2 |
Myeloid differentiation primary response 88 | MyD88 |
Interleukin-1 receptor accessory protein | IL1RAcP |
Interleukin-1 receptor-associated kinase | IRAK |
Tumor necrosis factor receptor-associated factor 6 | TRAF6 |
Nuclear factor-kappa B | NF-κB |
epidermal growth factor receptor | EGFR |
abdominal aortic aneurysm | AAA |
Full-length IL-33 | flIL-33 |
O-GlcNAc transferase | OGT |
Signal transducer and activator of transcription 6 | STAT6 |
Ubiquitin-specific peptidase 17 | USP17 |
Human embryonic kidney 293T | HEK293T |
Intercellular adhesion molecule 1 | ICAM-1 |
Vascular cell adhesion molecule 1 | VCAM-1 |
Runt-related transcription factor 2 | RUNX2 |
Mothers against decapentaplegic homolog 6 | Smad6 |
Transforming growth factor | TGF-beta |
Chemokine (C-C motif) Ligand 2 | CCL2 |
intercellular cell adhesion molecule-1 | ICAM1 |
interferon | IFN |
Regenerating Islet-Derived Protein 3 Gamma | REG3γ |
Extracellular signal-regulated kinase 1/2 | ERK1/2 |
Intestinal epithelial cells | IEC |
microRNA | miRNA |
Mucin 2 | MUC2 |
Amphiregulin | AREG |
Peroxisome proliferator-activated receptor gamma | PPARγ |
Immunoglobulin A | IgA |
Interleukin-1 receptor antagonist | IL-1Ra |
Lipopolysaccharide | LPS |
Senescence-accelerated prone mouse | SAMP |
Specific pathogen-free-SMAP | SPF-SAMP |
Germ-free-SAMP | GF-SAMP |
recombinant Interleukin-33 | rIl-33 |
Activated eosinophils | A-Eos |
Regulatory T cells | Tregs |
Forkhead Box P3 | Foxp3 |
Thymic stromal lymphopoietin | TSLP |
Toll-like receptor | TLR |
Mast cell protease 4 | MCPT4 |
Heat shock protein | Hsp |
F-box and leucine-rich repeat protein 19 | FBXL19 |
Tumor necrosis factor receptor-associated factor 6 | TRAF6 |
Nucleotide-binding oligomerization domain-containing protein 2 | NOD2 |
Peripheral blood mononuclear cells | PBMCs |
Dextran sodium sulfate | DSS |
2,4,6-Trinitrobenzenesulfonic acid | TNBS |
Transient receptor potential ankyrin 1 | TRPA1 |
Phospholipase C-gamma 1 | PLC-γ1 |
5-Hydroxytryptamine | 5-HT |
H. polygyrus alarmin release inhibitor | HpARI |
H. polygyrus binds alarmin receptor and inhibits | HpBARI |
Subepithelial myofibroblasts | SEMFs |
Vascular endothelial growth factor C | VEGFC |
T-Box expressed in T cells | T-bet |
Azoxymethane | AOM |
Tumor-associated macrophages | TAMs |
Prostaglandin E2 | PGE2 |
Colorectal Cancer | CRC |
Nuclear factor, erythroid 2 like 3 | NFE2L3 |
Double homeobox 4 | DUX4 |
Cyclin-dependent kinase 1 | CDK1 |
Ras-related protein RAB27 | RAB27 |
Mitogen-activated protein kinase | MAPK |
Focal adhesion kinase | FAK |
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Related Diseases or Cells | Mechanism | Refs. | |
---|---|---|---|
miR-487b | Chronic heart failure | Inhibits the expression of IL-33 and ST2. | [138] |
IL-37D | Obesity and metabolic disorders | Inhibits the production of sST2 in white adipose tissue (WAT) via the IL-1R8 receptor, upregulating IL-33/ST2 signaling. | [140] |
p38α/β MAPK pathway | ILC2 | Inhibits the p38α/β MAPK pathway, reduces the sensitivity of ILC2 to IL-33, and inhibits the production of type 2 cytokines. | [141] |
Notch1 signaling pathway | B cells | Upregulates the expression of IL-33 in B cells, hence regulating T cell immune response. | [142] |
Focal adhesion kinase (FAK) | Squamous cell carcinoma cells (SCCs) | FAK upregulates the expression of IL-33 and sST2 via RUNX1 and SP1. | [50] |
SPRR3 | Allergic asthma | Reduces the expression of IL-33, attenuating the activation of the PI3K/AKT/NF-κB signaling pathway in ILC2, and inhibiting allergic airway inflammation. | [139] |
Function | Related Diseases or Cells | Mechanism | Refs. | |
---|---|---|---|---|
Resveratrol | Inhibitor | Allergic disease | Inhibits IL-33/ST2-mediated mast cell activation by targeting the MK2/3-PI3K/Akt pathway downstream of p38 instead of the NF-κB pathway. | [143] |
Honokiol | Inhibitor | Lupus nephritis (LN) | Downregulates the expression of NLRP3 and ST2 to inhibit abnormal interaction between renal tubular epithelial cells and renal macrophages. | [144] |
HpBARI_Hom2 | Inhibitor | ? | Binds, with high affinity, to human ST2 to inhibit the binding of IL-33 to ST2. | [120] |
HpARI | Inhibitor | ? | Binds to IL-33 and prevents the binding of active IL-33 to ST2. | [88] |
HpARI_CCP1/2 | Activator | ? | Capable of stabilizing IL-33, increasing its half-life, and amplifying its effects. | [147] |
Tranilast | Inhibitor | Allergic disease | Tranilast significantly inhibits LPS-induced Akt activation and downregulates the expression of IL-33. | [145] |
Statins | Activator | Cardiovascular diseases | Inhibits the mevalonate (MAV) pathway, suppressing the geranylgeranylation of RhoA, leading to the inhibition of ROCK and the inactivation of SRF, thereby relieving SRF-mediated transcriptional repression of IL-33 gene expression and upregulating IL-33 expression. | [148] |
Flagellin of AIEC | Activator | Intestinal fibrosis | Promotes the expression of ST2 in IEC, activates the IL-33-ST2 pathway, and enhances intestinal fibrosis in the context of colitis. | [146] |
EF24 | Inhibitor | ? | Upregulates the expression of ST2 and SIGIRR, reduces the interaction between ST2 and MyD88, and significantly downregulates the expression of IL-33 in LPS-stimulated DCs. | [100] |
PPARγ | Activator | Colorectal Cancer | Promotes the secretion of IL-13 by ILC2s, thereby facilitating tumor migration and invasion. | [72] |
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Wang, Y.; He, C.; Xin, S.; Liu, X.; Zhang, S.; Qiao, B.; Shang, H.; Gao, L.; Xu, J. A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut. Int. J. Mol. Sci. 2023, 24, 13504. https://doi.org/10.3390/ijms241713504
Wang Y, He C, Xin S, Liu X, Zhang S, Qiao B, Shang H, Gao L, Xu J. A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut. International Journal of Molecular Sciences. 2023; 24(17):13504. https://doi.org/10.3390/ijms241713504
Chicago/Turabian StyleWang, Yi, Chengwei He, Shuzi Xin, Xiaohui Liu, Sitian Zhang, Boya Qiao, Hongwei Shang, Lei Gao, and Jingdong Xu. 2023. "A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut" International Journal of Molecular Sciences 24, no. 17: 13504. https://doi.org/10.3390/ijms241713504