Environmental Health Perspectives 105, Supplement 5, September 1997

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Particulate-Cell Interactions and Pulmonary Cytokine Expression

Jacob N. Finkelstein, 1,2,3 Carl Johnston, 1 Ted Barrett, 3 and Günter Oberdörster 3

1 Departments of Pediatrics, 2 Radiation Oncology, and 3 Environmental Medicine, University of Rochester School of Medicine, Rochester, New York

Abstract
The type II cell plays an important role in the response of the alveolar epithelium after lung injury through its synthesis and secretion of pulmonary surfactant, and by acting as the stem cell for the replacement of damaged type I epithelial cells. The nonciliated bronchiolar epithelial (Clara) cell is thought to play a similar role during repair of the bronchiolar epithelium. Recent evidence has suggested that epithelial cells may participate in aspects of the inflammatory response and regulation of fibroblast growth during pulmonary fibrosis through the production of and response to specific growth factors and cytokines. The cellular and molecular responses of epithelial cells and how they lead to the progression of events that defines the pulmonary parenchymal response to a class of particles is unclear. We used particles differing in size, chemical composition, and fibrogenicity in vivo and in vitro to elucidate early changes in proinflammatory and profibrotic cytokine and antioxidant gene expression in lung cells. Early increases in mRNA and protein for the proinflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha have been observed in epithelial cells following exposure. These are accompanied by changes in specific epithelial genes including surfactant protein C and Clara cell secretory protein. The data indicate that effects on the epithelium are due to direct interactions with particles, not a result of macrophage-derived mediators, and suggest a more significant role in the overall pulmonary response than previously suspected. These results suggest that type II cell growth factor production may be significant in the pathogenesis of pulmonary fibrosis. -- Environ Health Perspect 105(Suppl 5):1179-1182 (1997)

Key words : lung, epithelium, inflammation, particulate, cytokine, TNF- alpha , IL-1ß, IL-6

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 20 June 1997.

The authors wish to thank C. Reed, L. Paulhamous, N. Corson, and P. Mercer for their technical assistance. This work was supported in part by HL 36543, ES 04872, CA 27791, CA 11051, ES 01247, National Aeronautics and Space Administration Specialized Center of Research and Training grant NAGW-2356, the Nickel Producers Environmental Research Association, and a Health Effects Institute contract.

Address correspondence to Dr. J.N. Finkelstein, Department of Pediatrics, Box 777, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642. Telephone: (716) 275-5948. Fax: (716) 256-2631. E-mail: finj@envmed.rochester.edu

Abbreviations used: Clara, nonciliated bronchioepithelial; IL, interleukin; LPS, lipopolysaccharide; MIP, macrophage inflammatory protein; PTFE, polytetrafluoroethylene; TGF, tumor growth factor; TNF, tumor necrosis factor.

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Last Update: October 31, 1997