Inhalation of organic dust is associated with the development of respiratory diseases such as bronchitis, hypersensitivity pneumonitis, asthma, and chronic obstructive pulmonary disease (COPD). Chronic inflammation due to increased cytokine production has been linked to the development and progression of respiratory diseases. Peroxisome proliferator-activated receptor gamma (PPAR-γ), a transcription factor belonging to the nuclear hormone receptor family, is known to modulate inflammatory responses. In this study, we investigated the involvement of PPAR-γ in the regulation of organic dust induction of inflammatory mediators in THP-1 macrophages. THP-1 monocytic cells were differentiated into macrophages using phorbol myristate acetate. The effects of PPAR-γ agonists and antagonists on the induction of IL-6 and TNF-a expression by poultry organic dust extract were investigated by ELISA and real-time qRT-PCR. The effects of PPAR-γ agonist 15d-PGJ2 on ROS production and activation of MAPKs and NF-kB and STAT-3 activation were investigated by DCFDA labeling and western blotting respectively. We found that PPAR-γ agonist 15d-PGJ2 potently inhibited dust extract induction of TNF-α and IL-6 proteins by reducing mRNA expression. 15d-PGJ2 inhibited ROS levels and NF-κB and STAT-3 activation while concomitantly activating MAPKs. These data indicated that the inhibitory effects of 15d-PGJ2 on TNF-α and IL-6 may be mediated via reduced ROS and NF-κB and STAT-3 activation, suggesting that PPAR-γ could be targeted to attenuate organic dust-induced lung inflammation.
Date of publication
Vijay Boggaram, Ph.D., Ramakrishna Vankayalapati, Ph.D., Pierre Neuenschwander, Ph.D., Osamu Sato, Ph.D.
Master of Science in Biotechnology
Nsiah, Peter, "PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA (PPAR-γ) REGULATION OF INDUCTION OF INFLAMMATORY MEDIATORS BY ORGANIC DUST IN THP-1 MACROPHAGE CELLS" (2023). Biotechnology Theses. Paper 9.