The IL1RN gene provides instructions for a protein involved in the body’s immune system. Located on chromosome 2, this gene helps manage immune responses that protect us from illness. Its role in modulating inflammation is noteworthy, as it balances immune reactions, preventing them from becoming excessive or harmful. Understanding this gene’s function and variations offers insights into how our bodies respond to health challenges.
What is IL1RN
The IL1RN gene, short for Interleukin-1 Receptor Antagonist, is a protein-coding gene. It serves as a blueprint for the production of the protein IL-1Ra. This protein belongs to the interleukin 1 cytokine family, a group of signaling molecules that play a part in immune and inflammatory processes.
The IL1RN gene is composed of six exons, which are its coding regions. There are four known isoforms of the IL-1Ra protein, produced through alternative splicing. One isoform is secreted, while the other three remain within cells. The secreted form of IL-1Ra is the most extensively studied for its role in modulating immune responses.
How IL1RN Influences the Immune System
The IL-1Ra protein acts as a natural inhibitor of Interleukin-1 (IL-1). IL-1 is a pro-inflammatory cytokine that helps initiate and amplify inflammatory responses. These responses are part of the body’s defense mechanisms, signaling a threat like infection or tissue damage.
IL-1Ra binds to the same cell surface receptors that IL-1 would normally bind to. Unlike IL-1, IL-1Ra does not activate these receptors or trigger the inflammatory cascade. By occupying these sites, IL-1Ra effectively blocks IL-1 from binding and sending its inflammatory signals. This competitive binding helps prevent or reduce excessive inflammation, maintaining balance within the immune system and protecting tissues from damage caused by an overactive inflammatory response.
Genetic Differences in IL1RN
Genetic variations, or polymorphisms, in the IL1RN gene lead to different versions called alleles. A common variation is a variable number tandem repeat (VNTR) polymorphism located in intron 2. This VNTR consists of an 86-base pair sequence that can be repeated a different number of times, leading to various alleles.
The most frequent alleles are allele 1 (four repeats) and allele 2 (two repeats). The presence of certain alleles, such as allele 2, has been associated with an increase in IL-1Ra protein found in the serum. These genetic differences can impact the overall level or activity of the IL-1Ra protein an individual produces. Consequently, these variations can influence the ability to regulate inflammation, potentially leading to different inflammatory responses when faced with similar immune challenges.
IL1RN and Disease
Imbalances in IL-1 activity, often influenced by variations in the IL1RN gene or its dysregulation, are connected to a range of human diseases. These conditions frequently involve altered inflammatory responses or issues with immune regulation.
In various cancers, IL1RN polymorphisms have been investigated for their association with susceptibility and prognosis. For instance, the IL1RN2 allele has been linked to an increased risk of gastric cancer in some populations. In cervical cancer, variant genotypes of IL1RN have been associated with an elevated risk. Studies on breast cancer have explored the association of IL1RN polymorphisms with disease risk, with some findings suggesting a role in progression.
In bladder cancer, reduced IL1RA expression has been observed in invasive forms, and IL1RN gene polymorphisms have been associated with susceptibility. For colorectal cancer, specific IL1RN polymorphisms have shown associations, particularly with early-stage localized disease. The IL1RN1 allele, in combination with certain IL1B alleles, has been linked to an increased risk of non-small cell lung cancer, while the IL1RN2 allele has been associated with a decreased risk in some populations. Research on brain tumors, specifically glioblastoma, indicates that IL-1beta, which IL-1Ra antagonizes, can promote tumor progression.
The IL1RN gene is also implicated in inflammatory conditions like septic shock, with certain variants influencing survival and susceptibility to the condition. These associations highlight the broad impact of IL1RN in modulating inflammatory pathways that contribute to disease development and progression.