Organic dust inhibits surfactant protein expression by reducing thyroid transcription factor-1 levels in human lung epithelial cells

Exposure to organic dust is a risk factor for the development of respiratory diseases. Surfactant proteins (SP) reduce alveolar surface tension and modulate innate immune responses to control lung inflammation. Therefore, changes in SP levels could contribute to the development of organic-dust-induc...

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Main Authors: Kartiga Natarajan, Keerthi Gangam, Velmurugan Meganathan, Koteswara R Gottipati, Courtney Mitchell, Vijay Boggaram
Format: Article
Language:English
Published: SAGE Publishing 2019-02-01
Series:Innate Immunity
Online Access:https://doi.org/10.1177/1753425919827360
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author Kartiga Natarajan
Keerthi Gangam
Velmurugan Meganathan
Koteswara R Gottipati
Courtney Mitchell
Vijay Boggaram
author_facet Kartiga Natarajan
Keerthi Gangam
Velmurugan Meganathan
Koteswara R Gottipati
Courtney Mitchell
Vijay Boggaram
author_sort Kartiga Natarajan
collection DOAJ
description Exposure to organic dust is a risk factor for the development of respiratory diseases. Surfactant proteins (SP) reduce alveolar surface tension and modulate innate immune responses to control lung inflammation. Therefore, changes in SP levels could contribute to the development of organic-dust-induced respiratory diseases. Because information on the effects of organic dust on SP levels is lacking, we studied the effects of dust from a poultry farm on SP expression. We found that dust extract reduced SP-A and SP-B mRNA and protein levels in H441 human lung epithelial cells by inhibiting their promoter activities, but did not have any effect on SP-D protein levels. Dust extract also reduced SP-A and SP-C levels in primary human alveolar epithelial cells. The inhibitory effects were not due to LPS or protease activities present in dust extract or mediated via oxidative stress, but were dependent on a heat-labile factor(s). Thyroid transcription factor-1, a key transcriptional activator of SP expression, was reduced in dust-extract-treated cells, indicating that its down-regulation mediates inhibition of SP levels. Our study implies that down-regulation of SP levels by organic dust could contribute to the development of lung inflammation and respiratory diseases in humans.
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spelling doaj.art-7b4b2a19d4f84981901bf5160fb016602022-12-22T03:00:39ZengSAGE PublishingInnate Immunity1753-42591753-42672019-02-012510.1177/1753425919827360Organic dust inhibits surfactant protein expression by reducing thyroid transcription factor-1 levels in human lung epithelial cellsKartiga NatarajanKeerthi GangamVelmurugan MeganathanKoteswara R GottipatiCourtney MitchellVijay BoggaramExposure to organic dust is a risk factor for the development of respiratory diseases. Surfactant proteins (SP) reduce alveolar surface tension and modulate innate immune responses to control lung inflammation. Therefore, changes in SP levels could contribute to the development of organic-dust-induced respiratory diseases. Because information on the effects of organic dust on SP levels is lacking, we studied the effects of dust from a poultry farm on SP expression. We found that dust extract reduced SP-A and SP-B mRNA and protein levels in H441 human lung epithelial cells by inhibiting their promoter activities, but did not have any effect on SP-D protein levels. Dust extract also reduced SP-A and SP-C levels in primary human alveolar epithelial cells. The inhibitory effects were not due to LPS or protease activities present in dust extract or mediated via oxidative stress, but were dependent on a heat-labile factor(s). Thyroid transcription factor-1, a key transcriptional activator of SP expression, was reduced in dust-extract-treated cells, indicating that its down-regulation mediates inhibition of SP levels. Our study implies that down-regulation of SP levels by organic dust could contribute to the development of lung inflammation and respiratory diseases in humans.https://doi.org/10.1177/1753425919827360
spellingShingle Kartiga Natarajan
Keerthi Gangam
Velmurugan Meganathan
Koteswara R Gottipati
Courtney Mitchell
Vijay Boggaram
Organic dust inhibits surfactant protein expression by reducing thyroid transcription factor-1 levels in human lung epithelial cells
Innate Immunity
title Organic dust inhibits surfactant protein expression by reducing thyroid transcription factor-1 levels in human lung epithelial cells
title_full Organic dust inhibits surfactant protein expression by reducing thyroid transcription factor-1 levels in human lung epithelial cells
title_fullStr Organic dust inhibits surfactant protein expression by reducing thyroid transcription factor-1 levels in human lung epithelial cells
title_full_unstemmed Organic dust inhibits surfactant protein expression by reducing thyroid transcription factor-1 levels in human lung epithelial cells
title_short Organic dust inhibits surfactant protein expression by reducing thyroid transcription factor-1 levels in human lung epithelial cells
title_sort organic dust inhibits surfactant protein expression by reducing thyroid transcription factor 1 levels in human lung epithelial cells
url https://doi.org/10.1177/1753425919827360
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