Early-Life Exposure to Lipopolysaccharide Induces Persistent Changes in Gene Expression Profiles in the Liver and Spleen of Female FVB/N Mice

Simple Summary This study aimed to examine the impact of lipopolysaccharide (LPS) on the gene expression patterns of insulin signaling, innate immunity, and adaptive immunity in the liver and spleen of mice. The findings demonstrate that prolonged and continuous exposure to endotoxemia during early life (at 35 days of age) can initiate molecular mechanisms that result in lasting alterations in gene expression associated with inflammation and adaptive immunity. These changes may contribute to the development of various chronic inflammatory diseases in the liver and spleen. The results indicate that exposing mice to chronic and continuous endotoxemia during early life (at 35 days old) for a duration of 6 weeks can trigger molecular mechanisms that induce lasting changes in gene expression. These changes are associated with inflammation and adaptive immunity and may play a role in the pathobiology of diverse chronic inflammatory diseases affecting the liver and spleen. The objective of this study was to investigate how subcutaneous (sc) lipopolysaccharide (LPS) administration affects the gene expression profiles of insulin signaling as well as innate and adaptive immunity genes in mouse livers and spleens. FVB/N female mice were randomly assigned to one of two treatment groups at 5 weeks of age: (1) a six-week subcutaneous injection of saline at 11 & mu;L/h (control-CON), or (2) a six-week subcutaneous injection of LPS from Escherichia coli 0111:B4 at 0.1 & mu;g/g body weight at 11 & mu;L/h. At 106 weeks (i.e., 742 days) after the last treatment, mice were euthanized. Following euthanasia, liver and spleen samples were collected, snap frozen, and stored at -80 & DEG;C until gene expression profiling. LPS upregulated nine genes in the liver, according to the findings (Pparg, Frs3, Kras, Raf1, Gsk3b, Rras2, Hk2, Pik3r2, and Myd88). With a 4.18-fold increase over the CON group, Pparg was the most up-regulated gene in the liver. Based on the annotation cluster analysis, LPS treatment upregulated liver genes which are involved in pathways associated with hepatic steatosis, B- and T-cell receptor signaling, chemokine signaling, as well as other types of cancers such as endometrial cancer, prostate cancer, and colorectal cancer. LPS increased the spleen expression of Ccl11, Ccl25, Il6, Cxcl5, Pparg, Tlr4, Nos2, Cxcl11, Il1a, Ccl17, and Fcgr3, all of which are involved in innate and adaptive immune responses and the regulation of cytokine production. Furthermore, functional analysis revealed that cytokine-cytokine receptor interaction and chemokine signaling pathways were the most enriched in LPS-treated mice spleen tissue. Our findings support the notion that early-life LPS exposure can result in long-term changes in gene expression profiling in the liver and spleen tissues of FVB/N female mice.

Automated summary

This study investigated the effects of lipopolysaccharide (LPS) on gene expression patterns related to insulin signaling, innate immunity, and adaptive immunity in the liver and spleen of mice. The findings suggest that prolonged exposure to endotoxemia during early life can lead to lasting changes in gene expression associated with inflammation and adaptive immunity, potentially contributing to the development of chronic inflammatory diseases in the liver and spleen. The results also indicate that chronic endotoxemia exposure in early life triggers molecular mechanisms that result in lasting alterations in gene expression, specifically related to inflammation and adaptive immunity in the liver and spleen.