Elovanoid 34 Reduces Proinflammatory Cytokines and Arrest the Expression of Genes That Drive Senescence, Autophagy, Unfolded Protein Response (UPR), Matrix Metalloproteinases (MMPs) and Inflammation in Human Nasal Cells Exposed to House Dust Mite (HDM): Therapeutic Potential in Allergy

Elovanoids (ELV) are novel lipid mediators synthesized from very long-chain (VLC) omega-3 (n-3) polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA) or eicosa-pentaenoic acid (EPA), by the elongase enzyme ELOVL4. ELV have been shown to play a funda-mental role in maintaining brain and retina function, neuroprotection, maintaining the skin's permeability barrier, and sperm function, among other important cellular processes. Furthermore, the methyl ester or sodium salt of ELV-N32 and ELV-N34 have been found to be efficient in re-duced infarct volumes, promoting cell survival and decreasing the alteration of the neurovascular unit in a model of ischemia due to occlusion of the middle cerebral artery. Their bioactivity in-cludes enhancing of anti-apoptotic and pro-survival protein expression combined with the downregulation of pro-apoptotic proteins. House dust mite (HDM) is the most prevalent indoor allergen, and HDM exposure is frequently the cause of allergic respiratory disease, including aller-gic rhinitis and allergic asthma in HDM sensitized individuals. In our study, human nasal epithe-lial cells (HNEpC) were used as an in vitro model for allergy. The cells were challenged with HDM (mixture of Dermatophagoides farinae and D. pteronyssinus extract), with or without treat-ment with ELV-34. Phosphate-buffered saline (PBS) (vehicle) and ELV-34 (500 nM) alone were used as the control. Our findings show that ELV-34 promotes cell viability and reduces cytotoxi-city upon HDM sensitization of HNEpC. ELV-34 treatment significantly reduces the levels of IL-6, IL-1β, IL-8, VEGF, ICAM1, CXCL1 and CCL2, restored the IL-10 level and diminishes the induc-tion of the transcription of inflammatory and senescence genes in HNEpC. Our data also shows that HDM triggered the expression of several key genes in human nasal epithelial cells, including autophagy, unfolded protein response (UPR), Matrix metalloproteinases (MMPs), senescence and inflammation markers. Together, our data reveal a novel pro-homeostatic and cell-protective li-pid-signaling mechanism in nasal epithelial cells that envision novel potential therapeutic targets for the treatment of allergies.