Transcriptome analysis reveals the role of the PCP pathway in fipronil and endotoxin-induced lung damage

Pandit, Arif Ahmad; Gandham, Ravi Kumar; Mukhopadhyay, Chandra Sekhar; Verma, Ramneek; Sethi, R. S.

doi:10.1186/s12931-019-0986-1

Cited by 16 publications

(25 citation statements)

References 78 publications

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“…Herbicide 2,4-D had been previously reported to cause lung injury [37]. Our previous work also showed long term dietary exposure to pesticide such as fipronil [7,38], ethion [10], lindane [9], imidacloprid [6] and indoxacarb [39] cause lung injury. In addition, similar to observations made with other pesticides [6,40,41], there was increase in blood TLC, neutrophils and lymphocytosis with the high dose alone Interestingly, integrin β1 promotes cell adhesion to the extracellular matrix and is associated with highly invasive and metastatic behaviour in SCLC [18].…”

Section: Discussionmentioning

confidence: 65%

“…We present new data indicating lung inflammation and SCLC pathway as the top most First, we wanted to understand whether exposure to 2,4-D alone or in combination with LPS causes lung inflammation. We used LPS exposure alone as a control and its exposure caused lung inflammation as reported previously [7,10]. We used a combination of BAL analyses and Total Histological Score (THS) to determine lung inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Agricultural workers especially those in animal confinement or grain handling buildings may potentially get exposed to both pesticides and environmental bacterial lipopolysaccharides (LPS) [5]. Previous studies from our laboratory indicate that endotoxin interaction with various classes of pesticides increases the pesticide induced lung damage [6][7][8][9][10]. LPS ligate TLR-4 to activate various signaling pathways including NF-kB leading to the production of inflammatory mediators and lung inflammation [11].…”

Section: Introductionmentioning

confidence: 99%

“…We report the first data that 2,4-D exposure dysregulates SCLC pathway with increased protein expression of Itgb1, NF-kB, p53 and Cdk6 and decreased expression of Apaf1. [7]. BAL fluid was centrifuged at 500g for 10 min at 4°C to collect pellet and supernatant.…”

Section: Introductionmentioning

confidence: 99%

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Exposures to 2,4-Dichlorophenoxyacetic Acid With or Without Endotoxin Upregulate Small Cell Lung Cancer Pathway

Kaur

Kumar

Singh

et al. 2020

Preprint

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Background: Pesticide residues in food and environment along with airborne contaminants such as endotoxins pose health risk. Although herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) has been associated with increased risk of lung cancers such as small cell lung cancer (SCLC) among agricultural workers, there are no data on the SCLC signaling pathway upon 2,4-D exposure alone or in combination with endotoxin. Methods: We exposed Swiss albino mice (N=48) orally to high (9.58 mg kg -1 ) and low (5.12 mg kg -1 ) dosages of 2,4-D dissolved in corn oil for 90 days followed by E. coli lipopolysaccharide (LPS) or normal saline solution (80µl/animal. Lung samples and broncho-alveolar fluid (BALF) were subjected to Total histological score (THS) and TLC and DLC analyses, respectively. We used microarray and bioinformatics tools for transcriptomic analyses and differentially expressed genes were analyzed to predict the top canonical pathways followed by validation of selected genes qPCR and immunohistochemistry. Results: Total histological score (THS) along with broncho-alveolar fluid (BALF) analyses showed lung inflammation following long term dietary exposure to high or low doses of 2,4-D individually or in combination with LPS. Microarray analysis revealed exposure to high dose of 2,4-D alone or with endotoxin upregulated 2178 and 2142 and downregulated 1965 and 1719 genes, respectively (p<0.05; minimum cut off 1.5 log fold change). The low dose alone or with LPS upregulated 2133 and 2054 and downregulated 1838 and 1625 genes, respectively. Bioinformatics analysis showed SCLC as topmost dysregulated pathway along with differential expression of Itgb1, NF-kB1, p53, Cdk6 and Apaf1. Immunohistological and qPCR analyses also supported the transcriptomic data. Conclusions: Taken together, the data show exposures to high and low dose of 2,4-D with/without LPS induced lung inflammation and altered pulmonary transcriptome profile with the involvement of the SCLC pathway. The data from the study provides the insights of the potential damage on lungs caused by 2,4-D and endotoxin interaction and helps to better understand the mechanism of this complex relation.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exposures to 2,4-Dichlorophenoxyacetic Acid With or Without Endotoxin Upregulate Small Cell Lung Cancer Pathway

Kaur

Kumar

Singh

et al. 2020

Preprint

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“…The studies regarding interaction of LPS and pesticide on cytokine expression [13]; apoptosis [14] and lung immunity [15] suggested synergistic effect of the combination of LPS with pesticide compared to pesticide alone. We have reported that LPS interacts with various classes of pesticides to alter the magnitude of pulmonary damage [2,[16][17][18][19][20][21] as well as genotoxicity [7,22]. Thus, exposure to LPS may deteriorate the health of ethion exposed subjects by exaggerating the harmful effects of ethion.…”

Section: Introductionmentioning

confidence: 99%

Study of ethion and lipopolysaccharide interaction on lung in a mouse model

Verma

Sethi

2020

Lab Anim Res

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Ethion is an organophosphate used commonly in India despite being banned in many other countries. The present study was designed to study the interaction of ethion and lipopolysaccharide (LPS) together on lung after single low dose ethion exposure. Mice (n = 20) were alienated into control and treatment groups (n = 10 each). The treatment group was orally fed ethion (8 mg/kg/animal/day) dissolved in corn oil. The animals (n = 5 each) from both the groups were challenged with 80 μg Escherichia coli lipopolysaccharide (LPS) intranasally and the remaining animals (n = 5 each) were administered normal saline solution after 24 h. Ethion along with LPS induced lung inflammation as indicated by increased neutrophils and total leukocyte count (TLC) in broncheoalveolar lavage fluid. Ethion induced histomorphological alterations in lung as shown by increased pulmonary inflammation score in histopathology. Real time PCR analysis showed that ethion followed by LPS resulted significant (p < 0.05) increase in pulmonary Toll-like receptor (TLR)-4 (48.53 fold), interleukin (IL)-1β (7.05 fold) and tumor necrosis factor (TNF)-α (5.74 fold) mRNA expression. LPS co-exposure suggested synergistic effect on TLR4 and TNF-α mRNA expression. Ethion alone or in combination with LPS resulted genotoxicity in blood cells as detected by comet assay. The data suggested single dietary ethion exposure alone or in conjunction with LPS causes lung inflammation and genotoxicity in blood cells.

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Multiple exposures to poultry barn air and lipopolysaccharide synergistically increase the pulmonary expression of TLR-4 and IL-1β

Kaur

Sethi

2019

Journal of Occupational Health

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Poultry farming has made outstanding progress in structure and operation in the last three decades by evolving from mere backyard endeavor to one of the most specialized businesses. The increasing demands for poultry products along with technological advances have revolutionized the role and the structure of poultry industry. 1 Presently, the poultry industry is the most organized sector in animal agriculture and is worth Euro 14 500 million. 2 This sector has provided employment to around millions of people. However, the poultry workers come across certain health problems, particularly respiratory disorders. 3

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Transcriptome analysis reveals the role of the PCP pathway in fipronil and endotoxin-induced lung damage

Cited by 16 publications

References 78 publications

Exposures to 2,4-Dichlorophenoxyacetic Acid With or Without Endotoxin Upregulate Small Cell Lung Cancer Pathway

Exposures to 2,4-Dichlorophenoxyacetic Acid With or Without Endotoxin Upregulate Small Cell Lung Cancer Pathway

Study of ethion and lipopolysaccharide interaction on lung in a mouse model

Multiple exposures to poultry barn air and lipopolysaccharide synergistically increase the pulmonary expression of TLR-4 and IL-1β

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