Oxidative stress induced by organic dust exposure promotes autocrine inflammatory signaling that drives cytokine/chemokine transcription and secretion in human bronchial epithelial cells

Organic dust (OD) from animal production facilities contains a complex mixture of microbial components (e.g. endotoxin), ammonia, urea, feed and fecal particles, proteases and other factors that cause significant risk to pulmonary health. In the present study pro-inflammatory effects of OD extracts (ODE) were investigated using human bronchial epithelial (hBE) cells. ODE stimulated ROS production and increased intracellular Ca 2+ (Ca 2+ i) which peaked and returned to baseline after two minutes, followed by a much smaller secondary increase that persisted for several minutes. Pretreatment with ROS scavengers (glutathione, N-acetylcysteine) strongly inhibited the ODE effect and induction of antioxidant enzyme expression with bardoxolone (100 nM for 24 hours) abolished the response. Both the initial and secondary increases in Ca 2+ i were blocked by YM254890 (a Gq alpha G-protein subunit inhibitor), indicating a role for Gq-receptor activation. Gq-receptor selective antagonists targeting the H1 histamine receptor, three leukotriene receptors (CysLT1, CysLT2 and BLT1) and the EP1 PGE2 receptor were all shown to inhibit calcium mobilization. Moreover, selective inhibitors of histidine decarboxylase, 5-lipoxygenase and cyclooxygenase (COX1 and COX2) also blocked the ODE response, demonstrating activation of endogenous inflammatory signaling pathways that lead to autocrine activation of these Gq coupled receptors. The increases in Ca 2+ i triggered PKC activation (PKC alpha, PKC delta) which stimulated transcription and expression of multiple cytokine/chemokine mRNAs (IL1 beta, IL6, IL8, IL-33, TNF alpha) within 2 hours after exposure. Furthermore, ELISA assays confirmed that ODE increased secretion of IL1 beta, IL6, IL8 and IL33, each with varying sensitivities to PKC alpha, PKC delta and NF-kB inhibitors. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.