(P30-004-23) Urolithins Rescue E-Cigarette Condensate Induced DAMPs Mediated Signaling

Objectives: Electronic cigarettes (e-cigarettes) have gained popularity as a substitute for conventional cigarettes. However, the potential health risks associated with e-cigarette use remain uncertain. Host-derived danger-associated molecular patterns (DAMPs) contribute to immune/inflammatory responses during exposure to various environmental pollutants or pathogens. High mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70) are two such DAMPs that serve as extracellular pro-inflammatory mediators which promote inflammation. Diet supplementation and nutrivention strategies for the treatment of inflammation and cancer are attractive because the implementation is relatively easy even with populations with reduced incomes and resources. Naturally occurring phenolic acids, ellagic acid (EA) Ellagitannins (ETs) are such compounds that have a promising future. Hence, we postulate that both Urolithin (Uro)-A and C (ET metabolites) can reverse the tobacco-flavored e-cig vapor condensate (TF-ECVC) dependent DAMPs mediated inflammation in A549 cells.

Methods: Human type II lung alveolar epithelial cells commonly called A549 cells were pre-treated with 5 μM Uro-A or Uro-C followed by air or (1%) TF-ECVC±N (6 mg/ml) challenge for 24hrs.

Results: Our experiments revealed that pretreatment with Uro-A or Uro-C abrogated ECVC-induced pro-inflammatory cytokines/chemokines; transcription of toll-like receptor 4 (TLR-4) and receptor for advanced glycation end products (RAGE). We also observed that Uro-A and Uro-C rescued ECVC-induced NF-kB activation and the degradation of IkB-α (NF-kB inhibitor) in A549 cells. Interestingly, urolithins also reversed ECVC-induced DAMPs (HMGB1 and HSP70) expression in lung epithelial cells.

Conclusions: Overall, our findings unveil an important regulatory role of ellagic acid metabolites in ECVC-induced inflammation.

Funding Sources: Grant support to SB from Flight Attendant Medical Research Institute (FAMRI- 123253_YCSA_Faculty), Institutional Development Award (IDeA) to SB from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM12345, and USDA-NIFA-CBG Award # 2020-38821-31128 to SB.