Scientific Session II- Basic Science in Laryngology
ALA016 - Low Concentration Glucocorticoids Reduce Inflammatory Gene Expression and Extracellular Matrix Cross-Linking in Human Vocal Fold Fibroblasts and Macrophages
Thursday, April 28, 2022
3:33 PM – 3:39 PM CT
Location: Landmark D
Ryosuke Nakamura, PhD; Renjie Bing, MD; Ryan C. Branski, PhD
Associate Research Scientist New York University Grossman School of Medicine
Background/Objective: Glucocorticoids (GC) are ubiquitous in laryngology and modulate multiple cell activities. Outcomes remain variable, suggesting an opportunity for enhanced GC treatment protocols. In the current study, we sought to characterize optimal concentration(s) at which glucocorticoids elicit favorable in vitro outcomes in fibroblasts and macrophages. Based on previous data from our group, we hypothesize GCs primarily mainly exhibit anti-inflammatory and anti-fibrotic effects at low concentrations, and higher concentration of GCs enhance undesirable fibrotic responses. Study design: In vitro.
Methods: Human vocal fold fibroblasts and macrophages derived from THP-1 monocytes were treated with 0.03-1000nM dexamethasone, 0.3-10000nM methylprednisolone, and 0.3-10000nM triamcinolone in combination with interferon-γ, tumor necrosis factor-α, and interleukin-4. TNF, IL1B, PTGS2, LOX, TGM2, and CCN2 mRNA expression were analyzed via real-time polymerase chain reaction.
Results: Expression of inflammatory genes, including TNF, IL1B, PTGS2, increased in response to interferon-γ and tumor necrosis factor-α in both cell types, and this response was inhibited by GCs. IL-4 induced LOX and TGM2 expression only in macrophages, and this response was inhibited by GCs. GCs upregulated CCN2 in both cells regardless of cytokine stimulation. EC50s of each GC for upregulation of CCN2 were higher than IC50s for the other genes.
Conclusion: Low concentration GCs may be beneficial to prevent inflammation and cross-linking of extracellular matrix. Beyond optimal concentrations, GCs may contribute to an additive fibrotic response.