In vitro models for the assessment of inflammatory and immuno-modulatory effects of the volatile organic compound chlorobenzene.
An in vitro cell culture system based on an air/liquid culture technique was developed which allows a direct exposure of cells to volatile chemicals without medium coverage. For the establishment of the experimental system, chlorobenzene was used as a model compound. Chlorobenzene is a volatile organic compound which is mainly used as a solvent. Beside other adverse health effects, chlorobenzene exposure has been shown to be associated with respiratory tract irritations, Th2 differentiation, and allergic sensitizations. Human peripheral blood mononuclear cells (PBMC) and lung epithelial cells (A549) were exposed to chlorobenzene via gas phase for 20 h. Additionally, PBMC were incubated with culture supernatants from exposed lung epithelial cells. High chlorobenzene concentrations (100 g/m(3)) induced IL-8 production in A549 cells, whereby lower concentrations (10 microg/m(3)-1 g/m(3)) stimulated the secretion of the monocyte chemoattractant protein-1 (MCP-1). A direct effect of chlorobenzene on the cytokine secretion of PBMC was not found. However, if PBMC were incubated with culture supernatants of exposed lung cells, an enhanced production of the Th2 cytokine IL-13 was observed. This induction was prevented in the presence of an anti-MCP-1 antibody. Our data suggest that chlorobenzene induces the production of inflammatory mediators in lung cells. The primary chlorobenzene caused release of MCP-1 in lung epithelial cells may secondarily result in a Th2 differentiation in T lymphocytes. These findings may contribute to the understanding of how chlorobenzene mediates the development of inflammatory reactions in the airways and contributes to the development of an allergic reactivity.
Lehmann
Irina
I
Department of Environmental Immunology, Helmholtz Centre of Environmental Research - UFZ, Permoserstrasse 15, 04318 Leipzig, Germany. irina.lehmann@ufz.de
Röder-Stolinski
Carmen
C
Nieber
Karen
K
Fischäder
Gundula
G
D019138:Antibodies, Blocking / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D002722:Chlorobenzenes / Q000633:toxicity*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D018793:Interleukin-13 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012997:Solvents / Q000633:toxicity*; D014835:Volatilization
D019138:Antibodies, Blocking; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D002722:Chlorobenzenes; D017077:Culture Media, Conditioned; D018793:Interleukin-13; D016209:Interleukin-8; D012997:Solvents; C031294:chlorobenzene