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Generalized pustular psoriasis
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
In 2011, a major achievement in understanding the etiology of GPP was the identification of homozygous or composite heterozygous loss-of-function mutations of interleukin (IL)-36RN, a gene belonging to the IL-1 family encoding the IL-36 receptor antagonist (IL-36Ra), through studies of familial or sporadic GPP cases.4,8 This IL-36Ra protein is responsible for tight control of the inflammatory cascade resulting from the interaction of three inflammatory IL-36 cytokines (Il-36α, β, and γ) with a specific, common receptor called IL-1Rp2, which subsequently leads to the recruitment of an accessory receptor chain common to the IL-1 receptor called IL-1RacP. The IL-36RN mutations described so far lead to the absence or at least to major alterations in the production of functional IL-36Ra protein, and then to subsequent uncontrolled activation of the nuclear factor kappa B (NF-κB) signaling pathway and further production and release of inflammatory mediators, including IL-8/CXCL8 (a neutrophil-recruiting chemokine), TNF-α, and IL-6. Of note, the IL-36 receptor is heavily expressed in keratinocytes, dendritic cells, and monocytes, all cellular subtypes that are highly represented in the skin. The identification of IL-36 dysregulation in GPP led to the acronymous definition of deficiency of IL-36 receptor antagonist (DITRA). Since its initial description, IL-36RN mutations have been reported not only in sporadic cases of GPP, but also in subsets of patients with palmoplantar pustulosis (PPP), ACH, and acute exanthematous generalized pustulosis (AGEP), but not in isolated plaque psoriasis.9 There is, however, clear evidence that IL-36 agonist cytokines, especially IL-36γ, are consistently upregulated in plaque psoriasis lesions, making this pathway an appealing therapeutic target across different psoriasis subtypes.10 Rare GPP cases have been associated with heterozygous mutation of the CARD14 gene,11 or AP1S3 innate immune response genes.12 Altogether, even if IL-36 appears to be the dominant dysregulated pathway in GPP, there is evidence for genetic heterogeneity, as only a small proportion of patients have homozygous mutations for IL-36RN.
The epithelium-derived inflammatory mediators of chronic rhinosinusitis with nasal polyps
Published in Expert Review of Clinical Immunology, 2020
Chengshuo Wang, Bing Yan, Luo Zhang
IL-1α and IL-1β are two different forms of IL-1; with different localization, maturation, and secretion. IL-1α exists in the cytoplasm and on the cell membrane, whereas IL-1β is a primary secretory form of IL-1 [114]. IL-1α and IL-1β can be secreted by epithelial cells, endothelial cells, eosinophils, DCs, monocytes, lymphocytes, neutrophils and macrophages, and exert their effects by activating the IL-1 type I receptor (IL-1RI) [23,115]. The IL-1 type II receptor (IL-1RII) acts as a decoy receptor to inhibit the activity of IL-1 [23]. The binding of IL-1RI and IL-1RAcP initiates the signaling by the recruitment of the adaptor molecule MyD88 and the activation of IRAK, followed by a variety of signaling pathway cascades, which up-regulate the expression of various inflammatory cytokines [23].
Association of C3953T transition in interleukin 1β gene with idiopathic male infertility in an Iranian population
Published in Human Fertility, 2019
Tayyebeh Zamani-Badi, Mohammad Karimian, Abolfazl Azami-Tameh, Hossein Nikzad
Data from the String database reveals that IL-1β interacts with 10 other molecules (Figure 3): (i) Interleukin 1 receptor accessory protein (IL1RAP); (ii) Interleukin 1 receptor, type I (IL1R1); (iii) Caspase 1, apoptosis-related cysteine peptidase (CASP1); (iv) Interleukin 1 receptor, type II (IL1R2); (v) Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1(NFKB1); (vi) Interleukin 18 (IL18); (vii) Interleukin 1, alpha (IL1A); (viii) Mitogen-activated protein kinase 14 (MAPK14); (ix) Jun proto-oncogene (JUN); and (x) FBJ murine osteosarcoma viral oncogene homolog (FOS).
Associations between IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, and HTRA1 rs11200638 gene polymorphisms and development of optic neuritis with or without multiple sclerosis
Published in Ophthalmic Genetics, 2020
Valdas Stonys, Miglė Lindžiūtė, Alvita Vilkevičiūtė, Greta Gedvilaitė, Loresa Kriaučiūnienė, Mantas Banevičius, Reda Žemaitienė, Rasa Liutkevičienė
The IL1RAP gene encodes the interleukin 1 receptor accessory protein (19). IL1RAP acts as a cytokine and signals inflammation in the body by acting upon macrophages, neutrophils, B cells, Th2 cells, eosinophils, basophils, and mast cells (20). This protein, together with IL-1 and the IL-1 receptor, plays an important role in the induction of acute-phase and proinflammatory protein synthesis during infection, tissue damage, or stress (20). Together, proteins IL1RAP and IL1RL1 interact with IL-33 cytokine and activate the production of type 2 cytokines from polarized Th2 cells (21).