Study reveals IL1A as a significant risk factor for gout patients
A study published in the recent issue of International Journal of Medical Sciences, establishes the critical role of the IL1A gene in the progression of gout, emphasizing its substantial diagnostic efficacy. Specifically, IL1A emerges as a key contributor to the exacerbation of inflammation associated with gout by influencing the Toll-like receptor pathway.
The investigation, led by Dr. Ling and collaborators, employed a rigorous approach utilizing the GSE199950-Differential Expressed Genes (DEGs) dataset and applying Weighted Gene Co-Expression Network Analysis (WGCNA) on GSE199950. Within the turquoise module, 83 DEGs were identified, and upon analysis, 62 genes were found to overlap, with a mere 11 exhibiting interconnectedness in the protein-protein interaction (PPI) network. Significantly, these genes exhibited increased expression in samples treated with monosodium urate (MSU), a hallmark feature of gout.
The researchers demonstrated that IL1A exhibited elevated expression levels in individuals diagnosed with gout, indicating its robust potential for clinical diagnostics in the context of this inflammatory disorder. Importantly, these clinical findings were corroborated by in vitro experiments. Specifically, experiments involving the knockdown of IL1A resulted in a reduction in the expression of pro-inflammatory cytokines and proteins associated with the Toll-like receptor signaling pathway. Notable components affected by IL1A suppression included TLR2, TLR4, and MyD88, highlighting the central role of IL1A in modulating key elements of the inflammatory cascade associated with gout.
As a member of the interleukin-1 cytokine family, IL1A stands out as a pleiotropic cytokine with implications in diverse immunological responses, inflammatory processes, and hematological activities. Macrophages produce this gene as a pre-protein in response to cellular injury. Subsequently, proteolysis transforms it into its active form, leading to cell death. Emerging data propose the presence of IL1A polymorphisms in conditions like rheumatoid arthritis and Alzheimer’s disease. Experimental studies further reveal that exposing cells to elevated concentrations of MSU results in the upregulation of IL1A, IL-1β, IL-8, and TNFα. Notably, when IL1A is selectively knocked down, the expressions of these cytokines diminish accordingly, underscoring the pivotal role of IL1A in modulating these inflammatory mediators.
IL1A emerges as a pivotal gene implicated in gout progression, with promising diagnostic potential. Its role in fueling gout-related inflammation through the Toll-like receptor pathway signifies a crucial breakthrough. The analysis underscores the intricate molecular interactions underlying the pathogenesis of gout. The identification of these genes and their interactions provides valuable insights into potential targets for diagnostic and therapeutic interventions in the management of gout.
Reference
Ling M, Gan J, Hu M, Pan F, Liu M. IL1A regulates the inflammation in gout through the Toll-like receptors pathway. Int J Med Sci. 2024;21(1):188–99.