Apiaceous Vegetable Consumption Mitigates the Negative Effects of Acrolein Exposure on Immune Response, Energy Production and Cytoskeleton-Related Gene Expression

Objectives: This study evaluated the protective effect of apiaceous vegetable (API) consumption (celery and parsnip) on acrolein (ACR) exacerbated lung pathologies in Apolipoprotein E knockout (ApoE–/–) mice utilizing RNA sequencing analysis to identify differentially expressed genes (DEGs) which were subjected to the bioinformatics prediction-based software, Ingenuity Pathway Analysis (IPA), to predict the activation or inhibition of canonical pathways between study groups. Methods: Thirty-three ApoE–/– mice were randomly allocated into one of three diet/ACR exposure groups: a genetic strain control (GEN group); ACR alone (ACR group); and an API 42% intervention (ACR+API 42% group). Mice in the ACR and ACR+API 42%-fed groups were exposed to ACR (0.5 mg/kg body weight/day) intranasally for four weeks; the GEN group were given normal saline. After intervention, mice were euthanized via CO2 and lung tissues RNA were extracted for RNA sequencing to identify DEGs between ACR versus GEN and ACR versus ACR+API 42% groups. IPA software was subsequently used to reveal mechanistic and physiologic implications of DEGs for each pairwise comparison. Results: DEGs between ACR versus GEN and ACR versus ACR+API 42% groups revealed that ACR group mice, as compared to GEN and ACR+API 42% groups, showed an upregulation of immune response genes, including immunoglobulin heavy variable-76 (Ighv-76) and Ighv-12 (log2 fold change (FC) = 7.61 and 8.93, respectively: ACR versus ACR+API 42% and log2FC = 10.55 and 8.87, respectively: ACR versus GEN). IPA analyses posited that, for the ACR versus GEN, immunoregulatory response pathways were activated (e.g., B cell receptor signaling), while energy production pathways were inhibited (e.g., oxidative phosphorylation). In ACR versus ACR+API 42%, ciliogenesis (e.g., actin cytoskeleton signaling and regulation of actin-based motility by Rho) and energy production pathways were inhibited. Conclusions: Together, these data indicate that API consumption mitigates the deleterious effects of ACR exposure, as evidenced by downregulation of genes involved in adaptive immunity and preservation or activation of energy production and ciliogenesis gene pathways. Funding Sources: N/A.