IL-1β-induced inflammatory stress modulates mitochondrial and metabolic gene expression in dermal fibroblasts.

BACKGROUND: Dermal fibroblasts are essential for maintaining skin homeostasis, extracellular matrix remodeling, and tissue repair. Persistent inflammation disrupts fibroblast function, promotes mitochondrial dysfunction, and impairs tissue regeneration. This study aimed to establish an in vitro inflammatory model using interleukin-1 beta (IL-1β) and investigate inflammation-associated mitochondrial alterations in human dermal fibroblasts using an integrated experimental and bioinformatic approach. METHODS AND RESULTS: Inflammation was induced by treating the cells with 10 ng/mL IL-1β. Cell viability was evaluated using the WST-8 assay, and mitochondrial function was assessed by measuring ATP production and intracellular reactive oxygen species (ROS) levels using DCFH-DA. Morphological alterations were examined using confocal microscopy and quantified using ImageJ software. The mRNA expression levels of mitochondrial metabolism-related genes (SOD2, PPM1K, ACSL1, CS, and TOMM20) were determined using quantitative real-time PCR (qRT-PCR). In addition, in silico bioinformatic analyses were performed to identify inflammation-associated mitochondrial target genes and validate the experimental findings. IL-1β stimulation altered the expression of genes involved in mitochondrial homeostasis. Increased SOD2 expression indicated an enhanced oxidative stress response, whereas reduced CS, ACSL1, and TOMM20 expression suggested impaired lipid metabolism and mitochondrial integrity. These transcriptional alterations were accompanied by decreased cell viability, reduced ATP production, increased ROS generation, and inflammation-associated morphological alterations. The experimental findings were consistent with the in silico analyses, supporting the biological relevance of the identified target genes. CONCLUSIONS: Collectively, these findings demonstrate that IL-1β induces mitochondrial dysfunction in dermal fibroblasts and establish a reliable inflammatory model for investigating mitochondrial mechanisms involved in skin aging, chronic wound healing, and other inflammation-related skin disorders.