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Dr. Johnston, Ph.D.[/caption]
MedicalResearch.com Interview with:
Nikki Johnston, Ph.D.
Professor of Otolaryngology and Communication Sciences & Microbiology and Immunology
Medical College of Wisconsin
Co-founder and Chief Scientific Officer, N-Zyme Biomedical Inc.
MedicalResearch.com: Please provide a summary of your findings in your Modulation of Pepsin-Mediated Inflammatory Responses in Vocal Cord Epithelial Cells by Amprenavir and how that is impacting your future research studies.
Dr. Johnston: In this study, we wanted to know whether pepsin — the key nonacid component of reflux — could trigger inflammatory signaling in vocal cord epithelial cells, and whether a pepsin inhibitor could reverse that response. We found that exposing human vocal cord cells to pepsin at neutral pH, mimicking the nonacidic conditions typical of laryngopharyngeal reflux (LPR), significantly increased the transcription factor HIF-2α along with the downstream inflammatory genes IL8, IL1B, and ICAM1. Co-treatment with amprenavir, a pepsin inhibitor and the active metabolite of fosamprenavir, reduced HIF-2α levels and significantly suppressed IL8, ICAM1, and TNF expression.
Interestingly, when we blocked HIF-2α's transcriptional activity directly, only IL1B expression was reduced; IL8 and ICAM1 were unaffected or even further increased. This tells us that HIF-2α is one contributor to pepsin-driven inflammation in the vocal cords, but not the whole story — pepsin is very likely activating several parallel stress pathways (NF-κB and MAPK signaling, among others) at the same time. For our future work, this reinforces that a single downstream pathway inhibitor is unlikely to fully quiet pepsin-induced inflammation, whereas a pepsin inhibitor acting further upstream, like amprenavir, has the potential to blunt several of these pathways at once. We are now examining whether similar mechanisms extend to pepsin's emerging role in pulmonary fibrotic disease and gastro-esophageal reflux disease (GERD).
