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

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Abstract

Animal production units produce and store many contaminants on-site, including organic dust (OD) and hydrogen sulfide (H2S). Workers in these settings report various respiratory disease symptoms. Both OD and H2S have shown to induce lung inflammation. However, impact of co-exposure to both H2S and OD has not been investigated. Therefore, we tested a hypothesis that pre-exposure to H2S modulates the innate inflammatory response of the lungs to organic dust. In a mouse model of H2S and organic dust extract (ODE) exposure, we assessed lung inflammation quantitatively. We exposed human airway epithelial and monocytic cells to medium or H2S alone or H2S followed by ODE and measured cell viability, oxidative stress, and other markers of inflammation. Exposure to 10 ppm H2S followed by ODE increased the lavage fluid leukocytes. However, exposure to 10 ppm H2S alone resulted in changes in tight junction proteins, an increase in mRNA levels of tlr2 and tlr4 as well as ncf1, ncf4, hif1α, and nrf2. H2S alone or H2S and ODE exposure decreased cell viability and increased reactive nitrogen species production. ODE exposure increased the transcripts of tlr2 and tlr4 in both in vitro and in vivo models, whereas increased nfkbp65 transcripts following exposure to ODE and H2S was seen only in in vitro model. H2S alone and H2S followed by ODE exposure increased the levels of IL-1β. We conclude that pre-exposure to H2S modulates lung innate inflammatory response to ODE.

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Acknowledgments

We would like to thank Dr. Locke A. Karriker (VDPAM, Iowa State University) for supplying us with OD samples. We would like to thank Dr. Jacek Koziel (Department of Agricultural and Biosystems Engineering, Iowa State University) for initial help with the measurement of H2S concentrations and the Department of Biomedical Sciences for providing access to the core laboratory facilities.

Funding

C.C. laboratory is currently funded through a startup grant from Iowa State University and seed grants from the College of Veterinary Medicine, Iowa State University. This manuscript was supported in part by Grant Number 5 U54 OH007548 from CDC—NIOSH.

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Authors and Affiliations

  1. Biomedical Sciences, Iowa State University, Ames, IA, 50011, USA

    Denusha Shrestha, Sanjana Mahadev Bhat, Nyzil Massey & Chandrashekhar Charavaryamath

  2. Immunobiology Interdepartmental Graduate Program, Iowa State University, Ames, IA, 50011, USA

    Sanjana Mahadev Bhat

  3. Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, 50011, USA

    Cristina Santana Maldonado

  4. Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA

    Wilson K. Rumbeiha

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  1. Denusha Shrestha
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Correspondence to Chandrashekhar Charavaryamath.

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441_2020_3333_MOESM1_ESM.tif

Supplementary file1: Fig. S1 H2S and ODE exposure induced histopathological changes in the lungs H&E images are shown in the left and inflammatory score is shown in the right. Histopathological changes due to exposure to either H2S or ODE or co-exposure to H2S and ODE were not significantly different among any of the groups. Compared with controls (a-c), ODE exposure of mice did not induce any morphological changes in the blood vessels, bronchioles and septa except for the number of club cells (b). (Micrometer bar = 100 µm). Data (mean ± SEM, n = 5–6/group) analyzed with one-way ANOVA followed by Tukey’s post hoc test for multiple comparisons as compared with 0 ppm (TIF 92 MB)

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Shrestha, D., Bhat, S.M., Massey, N. et al. Pre-exposure to hydrogen sulfide modulates the innate inflammatory response to organic dust. Cell Tissue Res 384, 129–148 (2021). https://doi.org/10.1007/s00441-020-03333-3

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