Pre-exposure to hydrogen sulfide modulates the innate inflammatory response to organic dust

Nrf2 Activation Protects Against Organic Dust and Hydrogen Sulfide Exposure Induced Epithelial Barrier Loss and K. pneumoniae Invasion

“…The chief contaminants within the animal feeding operations settings include airborne organic dust, gases such as hydrogen sulfide (H 2 S) and other volatile organic compounds ( Iowa State University and University of Iowa, 2002 ; Ni et al., 2012 ). Workers in the animal production settings are persistently exposed to airborne organic dust containing microbes and microbial products as well as gases such as H 2 S ( Iowa State University and University of Iowa, 2002 ; Shrestha et al., 2021 ). Exposed individuals report both acute and chronic respiratory symptoms such as coughing, sneezing, bronchitis, chest-tightness, asthma and asthma-like symptoms, mucus membrane irritation, chronic obstructive pulmonary disease (COPD), with a decline in lung function ( Sahlander et al., 2012 ; Sethi et al., 2017 ; Nordgren and Charavaryamath, 2018 ).…”

“…Therefore, understanding how a combined exposure to organic dust and H 2 S would alter homeostasis of respiratory system is important. Our recent work ( Shrestha et al., 2021 ) using a mouse model showed that a single pre-exposure to H 2 S altered the host response to organic dust. Notably, H 2 S pre-exposure or H 2 S+ODE exposure decreased cell viability, increased the transcripts of tlr2 and tlr4 as well as oxidative stress and inflammation markers.…”

“…Organic dust extracts (ODE) from animal feeding operations induce a profound inflammatory response both in vitro and in vivo with several prior studies demonstrating strong roles for Toll-like receptor (TLR) and MyD88 signaling pathways ( Charavaryamath et al., 2005 ; Charavaryamath et al., 2008 ; Charavaryamath et al., 2008 ; Poole et al., 2015 ). In airway epithelial cells, these exposures induce pro-inflammatory cytokine release, neutrophil influx, mucus metaplasia, alter tight junction expressions, disrupt cellular migration, and slow ciliary beat frequency ( Wyatt et al., 2008 ; Bhat et al., 2019 ; Johnson et al., 2020 ; Shrestha et al., 2021 ). It has also been demonstrated that CO 2 concentrations differentially effect the magnitude of inflammatory responses to ODE and various TLR ligands ( Schneberger et al., 2015 ; Schneberger et al., 2021 ).…”

“…Other occupational toxicants including particulate matter (PM) exposure result in increases in Pseudomonas aeruginosa infectivity due to disruption of airway epithelial barrier ( Liu et al., 2019 ). We recently demonstrated that ODE and H 2 S exposure induced Nuclear factor-erythroid factor 2-related factor 2 ( Nrf2 ) gene expression in monocytes and airway epithelial cells with associated decreased cell viability and increased reactive nitrogen species production ( Shrestha et al., 2021 ). However, it is not known whether Nrf2 activity can be targeted to reverse adverse effects and whether exposure-induced airway epithelial cell dysfunction is associated with enhanced infection susceptibility to inform future strategies.…”

“…H 2 S and organic dust exposures induce an overwhelming oxidative stress response. Host cells respond to the oxidative stress via activation of the Nrf2 pathway ( Shrestha et al., 2021 ). In the absence of an effective antioxidant response, unchecked release of reactive oxygen species (ROS), reactive nitrogen species (RNS) and inflammatory cytokines would result in lung homeostasis imbalance.…”