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

Koteswara R Gottipati; Shiva Kumar Bandari; Matthew W Nonnenmann; Jeffrey L Levin; Gregory P Dooley; Stephen J Reynolds; Vijay Boggaram

doi:10.1152/ajplung.00215.2014

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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

Journal article

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Peer reviewed

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

Koteswara R Gottipati, Shiva Kumar Bandari, Matthew W Nonnenmann, Jeffrey L Levin, Gregory P Dooley, Stephen J Reynolds and Vijay Boggaram

American journal of physiology. Lung cellular and molecular physiology, Vol.308(1), pp.L11-L21

01/01/2015

DOI: 10.1152/ajplung.00215.2014

PMCID: PMC4281698

PMID: 25398986

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Abstract

Exposure to the agricultural work environment is a risk factor for the development of respiratory symptoms and chronic lung diseases. Inflammation is an important contributor to the pathogenesis of tissue injury and disease. Cellular and molecular mechanisms mediating lung inflammatory responses to agricultural dust are not yet fully understood. We studied the effects of poultry dust extract on molecular regulation of interleukin-8 (IL-8), a proinflammatory cytokine, in A549 and Beas2B lung epithelial and THP-1 monocytic cells. Our findings indicate that poultry dust extract potently induces IL-8 levels by increasing IL-8 gene transcription without altering IL-8 mRNA stability. Increase in IL-8 promoter activity was due to enhanced binding of activator protein 1 and NF-κB. IL-8 induction was associated with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activation and inhibited by PKC and MAPK inhibitors. IL-8 increase was not inhibited by polymyxin B or l-nitroarginine methyl ester, indicating lack of involvement of lipopolysaccharide and nitric oxide in the induction. Lung epithelial and THP-1 cells share common mechanisms for induction of IL-8 levels. Our findings identify key roles for transcriptional mechanisms and protein kinase signaling pathways for IL-8 induction and provide insights into the mechanisms regulating lung inflammatory responses to organic dust exposure.

Cell Line, Tumor

Dust

Epithelial Cells - metabolism

Epithelial Cells - pathology

Gene Expression Regulation - drug effects

Humans

Interleukin-8 - biosynthesis

MAP Kinase Signaling System - drug effects

Monocytes - metabolism

Monocytes - pathology

Protein Kinase Inhibitors - pharmacology

Respiratory Mucosa - metabolism

Respiratory Mucosa - pathology

Transcription, Genetic - drug effects

Details

Title: Subtitle: Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells
Creators: Koteswara R Gottipati - Department of Cell and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas
Shiva Kumar Bandari - Department of Cell and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas
Matthew W Nonnenmann - Department of Occupational Health Sciences, University of Texas Health Science Center at Tyler, Tyler, Texas
Jeffrey L Levin - Department of Occupational Health Sciences, University of Texas Health Science Center at Tyler, Tyler, Texas
Gregory P Dooley - Center for Environmental Medicine, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado
Stephen J Reynolds - High Plains Intermountain Center for Agricultural Health and Safety, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado
Vijay Boggaram - Department of Cell and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas; vijay.boggaram@uthct.edu
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.308(1), pp.L11-L21
DOI: 10.1152/ajplung.00215.2014
PMID: 25398986
PMCID: PMC4281698
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Grant note: P30 ES005605 / NIEHS NIH HHS U54 OH007541 / NIOSH CDC HHS
Language: English
Date published: 01/01/2015
Academic Unit: Occupational and Environmental Health; Internal Medicine
Record Identifier: 9984214947002771

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