Investigating minocycline’s anti-inflammatory role in alveolar macrophages
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Issue Date
2023-08
Authors
Scholl, Erica '23
Degree
Advisor
Shakerley, Nicole
Committee Members
Parent, Michelle
Butler, David
Jayachandran, Pradeepa
Butler, David
Jayachandran, Pradeepa
Journal Title
Journal ISSN
Volume Title
Abstract
Minocycline has been FDA-approved for 50 years and is utilized to treat a wide range of infections. More recently, minocycline has been used to treat several sterile inflammatory conditions due to its non-antimicrobial anti-inflammatory properties. While minocycline is a unique and beneficial therapeutic, its immunomodulatory impact on inflammation during an active infection is not well understood. Elucidating the molecular mechanism of minocycline’s ability to modulate the inflammatory response can lead to the development of novel therapeutic strategies that take advantage of the antibiotic capabilities of minocycline while also protecting the host against post-infection inflammatory tissue damage. We hypothesized that minocycline exerts anti-inflammatory properties that suppress the cytokine production after macrophage activation, altering the host immune response to pathogens and limiting tissue damage. Our data indicates that minocycline is nontoxic to alveolar macrophages even at doses far beyond therapeutic potential. Additionally, pretreatment with minocycline significantly decreased the activation of nuclear factor kappa beta (NF-κB), as well as the secretion of several inflammatory cytokines following treatment with ligands to activate specific toll-like receptors. Total levels of key signaling molecules MyD88 and NF-κB were not altered following minocycline pretreatment, suggesting that minocycline may be altering the activation status within the cascade. Lastly, the pretreatment of macrophages with minocycline appears to have no significant effect on the production of oxidative stress following ligand treatment at 24 hours. Our long-term goal is to identify immunomodulatory mechanisms exerted by minocycline in the presence of an infection, as it could be the key to managing infections by not only eliminating the pathogen but also minimizing host inflammatory tissue damage, which is a driver of poor patient outcomes.
Citation
Scholl E. Investigating minocycline's anti-inflammatory role in alveolar macrophages. Ann Arbor (MI): Proquest LLC; 2023. 53 p.
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