Perspective - (2022) Volume 16, Issue 1
Date of Submission: 05-Jan-2022, Manuscript No. jmgm-22-52701;
Editor assigned: 07-Jan-2022, Pre QC No. P-52701;
Reviewed: 12-Jan-2022, QC No. Q-52701;
Revised: 17-Jan-2022, Manuscript No. R- 52701;
, DOI: 10.37421/1747-0822.214.171.1246
Citation: Priyadarshini, Veena. “Interleukin-1 Deficiency Disorders and its Molecular Mechanism.” J Mol Genet Med 16(2022): 526. DOI: 10.37421/1747-08126.96.36.1996.
Copyright: © 2022 Priyadarshini V. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DIRA (Deficiency of the Interleukin Receptor Antagonist) is a relatively rare hereditary autoinflammatory condition that manifests in infancy. The significant inflammatory response is like an acute severe systemic infection or a bone infection. Treatment with anakinra, a biologic drug, can prevent death from multiorgan failure if caught early. Only a handful of children have been diagnosed with DIRA. It appears shortly after birth or throughout the first few days of life. Families from Puerto Rico, Newfoundland (Canada), the Netherlands, and Lebanon have all been identified as having cases. DIRA is an autosomal recessive genetic illness, which means that each kid of two carriers has a 25% chance of developing the disease. DIRA is caused by homozygous point mutations in the IL1RN gene (2q14.2) or a substantial genomic loss on chromosome 2 that affects this and other IL family genes. The same mutation is identified in all patients from the same region, implying that each location has its own founder effect. Carrier frequencies for the mutation were reported to be 0.2 percent in Newfoundland and 1.3 percent in Puerto Rico in studies of normal controls from the same areas. When these mutations are homozygous, no functional interleukin-1 receptor antagonist protein is produced. As a result, interleukin-1 has no antagonistic effects on the receptor. Interleukin-1 receptor stimulation is a potent inflammatory pathway activator. The symptoms of this syndrome appear at birth or within days of delivery and are caused by inflammatory changes in the skin and bone in the absence of fever. Fetal discomfort, pustular rash, mouth sores, joint swelling, painful movement, and liver and spleen enlargement are all common presenting signs in the early days of life (hepatosplenomegaly) [1,2] .
The IL1RN gene's proper function is affected by the mechanism of interleukin-1–receptor antagonist deficiency. Interleukin 1(alpha) and interleukin 1(beta) are inhibited by the protein generated by the IL1RN gene (beta). As a result, immunological and inflammatory responses that are pathophysiologic are suppressed. The (IL1RN*1) and (IL1RN*2) alleles of the interleukin 1 receptor antagonist (IL1RN) are the most prevalent, with the remaining alleles accounting for less than 5% of the population. IL-1RN interacts to the same cell receptors as IL-1 and inhibits its inflammatory effects. The body can't manage IL-1-induced systemic inflammation without IL-1Ra. DIRA is resistant to antibiotics. IL-1 causes cartilage breakdown and bone erosion by activating synoviocytes and chondrocytes to create tiny inflammatory mediators (e.g., prostaglandins) and matrix metalloproteases (MMPs) [3,4]. The expression of receptor-associated NF-B ligand (RANK ligand) is also increased by IL-1, which leads to osteoclast development and activation, as well as bone degradation. It works by binding to the IL-1 receptor, as well as signaling and the production of various molecules and cytokines by cells. The IL-1 receptor antagonist (IL-1Ra) is an acute phase anti-inflammatory protein that is found in nature and belongs to the IL-1 supergene family. IL-1 controls a variety of innate immune processes, making it a master regulator of inflammation. IL-1 has a long history of biological roles, including operating as a leukocytic pyrogen, a mediator of fever and a leukocytic endogenous mediator, as well as an inducer of various components of the acute-phase response and lymphocyteactivating factor (LAF). In addition, serum blocking factors identified by the leukocyte adherence inhibition test in breast cancer patients were described. IL-1 controlled the serum adherence-promoting factors.
There are two unique versions of IL-1, which are isolated from two different cDNAs but have identical biological activities. Although the amino acid sequence homology between IL-1 and IL-1 is low (27 percent), the two proteins are structurally similar and perform the same functions because they share a common receptor, the IL-1 type 1 receptor (IL-1R1), and both have the same central -barrel and adjoining loops. To date, the tumor microenvironment has been characterized by dominant immunosuppression, with tumor immunosuppressive myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and tumor-associated macrophages (TAMs) infiltrating the tumor microenvironment. TAMs and MDSCs, which promote tumor formation in breast cancer, can be recruited by IL-1. The distinction between IL-1 and IL-1 is a 14-residue N-terminal extension beyond the N-terminus of both proteins. Each precursor has a molecular weight of around 31 kDa, and IL-1 and IL-1 are processed into mature forms by specific proteases. The nuclear localization sequence (NLS) and transcription activity are found in the N-terminal domain of IL-1. A 271-amino-acid (AA) precursor protein is used to make IL-1. Sp1 activates the IL-1 promoter activity in the 5′-upstream GC box (60 to 45 bp) for transcription of the IL-1 gene, and NF-B, which is also activated by IL-1, stimulates the consensus promoter region (103 to 70 bp) to induce its own gene expression and production in an autocrine way .