Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells

Gottipati, Koteswara R.; Bandari, Shiva Kumar; Nonnenmann, Matthew W.; Levin, Jeff; Dooley, Gregory P.; Reynolds, Stephen J.; Boggaram, Vijayakumar

doi:10.1152/ajplung.00215.2014

Cited by 15 publications

(50 citation statements)

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“…Lung epithelial cells produce chemokines, cytokines and other bioactive molecules in response to environmental agents to modulate host inflammatory and immune responses [ 11 – 13 ]. We found previously that lung epithelial and THP-1 cells express high levels of interleukin-8 (IL-8) in response to poultry dust extract treatment, and protein kinase signaling and transcriptional mechanisms mediate IL-8 induction [ 14 ]. Our studies also demonstrated that polymyxin B did not block induction of IL-8 expression indicating that endotoxin in dust extract may not act independently as an inducing agent [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…We found previously that lung epithelial and THP-1 cells express high levels of interleukin-8 (IL-8) in response to poultry dust extract treatment, and protein kinase signaling and transcriptional mechanisms mediate IL-8 induction [ 14 ]. Our studies also demonstrated that polymyxin B did not block induction of IL-8 expression indicating that endotoxin in dust extract may not act independently as an inducing agent [ 14 ]. Our studies on the effects of poultry dust extract on gene expression profiling showed that several cytokine, chemokine and inflammatory proteins are commonly up-regulated in lung epithelial and THP-1 cells [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Proteases and oxidant stress control organic dust induction of inflammatory gene expression in lung epithelial cells

et al. 2016

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BackgroundPersistant inflammatory responses to infectious agents and other components in organic dust underlie lung injury and development of respiratory diseases. Organic dust components responsible for eliciting inflammation and the mechanisms by which they cause lung inflammation are not fully understood. We studied the mechanisms by which protease activities in poultry dust extracts and intracellular oxidant stress induce inflammatory gene expression in A549 and Beas2B lung epithelial cells.MethodsThe effects of dust extracts on inflammatory gene expression were analyzed by quantitative polymerase chain reaction (qPCR), enzyme linked immunosorbent (ELISA) and western blot assays. Oxidant stress was probed by dihydroethidium (DHE) labeling, and immunostaining for 4-hydroxynonenal (4-HNE). Effects on interleukin-8 (IL-8) promoter regulation were determined by transient transfection assay.ResultsDust extracts contained trypsin and elastase activities, and activated protease activated receptor (PAR)-1 and -2. Serine protease inhibitors and PAR-1 or PAR-2 knockdown suppressed inflammatory gene induction. Dust extract induction of IL-8 gene expression was associated with increased DHE-fluorescence and 4-HNE staining, and antioxidants suppressed inflammatory gene induction. Protease inhibitors and antioxidants suppressed protein kinase C and NF-κB activation and induction of IL-8 promoter activity in cells exposed to dust extract.ConclusionsOur studies demonstrate that proteases and intracellular oxidants control organic dust induction of inflammatory gene expression in lung epithelial cells. Targeting proteases and oxidant stress may serve as novel approaches for the treatment of organic dust induced lung diseases. This is the first report on the involvement of oxidant stress in the induction of inflammatory gene expression by organic dust.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0455-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proteases and oxidant stress control organic dust induction of inflammatory gene expression in lung epithelial cells

et al. 2016

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“…Our observation suggests that this type of immune responses may preferentially occur in Sy+/Se− workers. The effect on IL-8 may also be explained by some component of organic dust 16. However, we cannot exclude that other agents (virus, bacteria, fungi, protozoa) were the cause of the increased IL-17A concentration.…”

Section: Discussionmentioning

confidence: 91%

Can serum cytokine profile discriminate irritant-induced and allergen-induced symptoms? A cross-sectional study in workers mostly exposed to laboratory animals

et al. 2017

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“…). However, the inhibition of endotoxin activity in agricultural dust did not attenuate the inflammatory response in lung epithelial cells nor human peripheral blood monocytes (Romberger et al ., ; Poole et al ., ; Gottipati et al ., ). Muramic acid, a marker of the bacterial cell wall component PGN and Gram‐positive bacteria, has a higher concentration in large animal agricultural dust ( i.e., swine and dairy ) than human house dust (Poole et al ., ).…”

Section: Discussionmentioning

confidence: 97%

“…Our results further suggest that Gram‐positive bacteria should be used for future mechanistic studies. Furthermore, the vast majority of studies elucidating the agricultural dust induced inflammatory mechanism in the respiratory tract have focused on aqueous or organic settled dust extracts (Poole et al ., ; Gottipati et al ., ). Our results demonstrate a significant difference of microbial diversity and abundance between airborne and settled poultry dust (Figs ).…”

Section: Discussionmentioning

confidence: 97%

High throughput genomic sequencing of bioaerosols in broiler chicken production facilities

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et al. 2016

Microbial Biotechnology

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SummaryChronic inhalation exposure to agricultural dust promotes the development of chronic respiratory diseases among poultry workers. Poultry dust is composed of dander, chicken feed, litter bedding and microbes. However, the microbial composition and abundance has not been fully elucidated. Genomic DNA was extracted from settled dust and personal inhalable dust collected while performing litter sampling or mortality collection tasks. DNA libraries were sequenced using a paired‐end sequencing‐by‐synthesis approach on an Illumina HiSeq 2500. Sequencing data showed that poultry dust is predominantly composed of bacteria (64–67%) with a small quantity of avian, human and feed DNA (< 2% of total reads). Staphylococcus sp. AL1, Salinicoccus carnicancri and Lactobacillus crispatus were the most abundant bacterial species in personal exposure samples of inhalable dust. Settled dust had a moderate relative abundance of these species as well as Staphylococcus lentus and Lactobacillus salivarius. There was a statistical difference between the microbial composition of aerosolized and settled dust. Unlike settled dust composition, aerosolized dust composition had little variance between samples. These data provide an extensive analysis of the microbial composition and relative abundance in personal inhalable poultry dust and settled poultry dust.

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Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells

Abstract: Gottipati KR, Bandari SK, Nonnenmann MW, Levin JL, Dooley GP, Reynolds SJ, Boggaram V. Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells.

Cited by 15 publications

References 59 publications

Proteases and oxidant stress control organic dust induction of inflammatory gene expression in lung epithelial cells

Proteases and oxidant stress control organic dust induction of inflammatory gene expression in lung epithelial cells

Can serum cytokine profile discriminate irritant-induced and allergen-induced symptoms? A cross-sectional study in workers mostly exposed to laboratory animals

High throughput genomic sequencing of bioaerosols in broiler chicken production facilities

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