Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells.
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.
Department of Cell and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas;
Koteswara R
KR
Gottipati
Department of Cell and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas;
Shiva Kumar
SK
Bandari
Department of Occupational Health Sciences, University of Texas Health Science Center at Tyler, Tyler, Texas;
Matthew W
MW
Nonnenmann
Department of Occupational Health Sciences, University of Texas Health Science Center at Tyler, Tyler, Texas;
Jeffrey L
JL
Levin
Center for Environmental Medicine, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado;
Gregory P
GP
Dooley
High Plains Intermountain Center for Agricultural Health and Safety, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado.
Stephen J
SJ
Reynolds
Department of Cell and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas; vijay.boggaram@uthct.edu.
Vijay
V
Boggaram
D045744:Cell Line, Tumor; D004391:Dust; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects*
C508606:CXCL8 protein, human; D004391:Dust; D016209:Interleukin-8; D047428:Protein Kinase Inhibitors
chemokine; lipopolysaccharide; lung inflammation