The diesel exhaust component pyrene induces expression of IL-8 but not of eotaxin.
Environmental pollutants can influence the expression of immunoregulatory molecules and, in this way, promote allergies. The local synthesis of proinflammatory chemokines is an important aspect in the development of allergic airway inflammation. We have characterized the influence of pyrene, a polycyclic aromatic hydrocarbon (PAH) contained, for example, in diesel exhaust particles (DEP), on transcription and secretion of the chemokines interleukin-8 (IL-8) and eotaxin. Reporter genes under control of the respective promoters were tested in the human cell lines A549 and HeLa, mRNA production was assayed in A549 cells and protein production was measured by ELISA in cell supernatants from primary human fibroblasts. Pyrene content of cell supernatants was measured by analytical HPLC. Promoter activity, mRNA production and protein expression of IL-8 were increased by pyrene. The activating effect in reporter gene studies was abolished by mutating either an NF-kappaB or an AP-1 binding site in the IL-8 promoter. In contrast, pyrene showed no effect on transcription from the eotaxin promoter, despite the important role of this chemokine in asthma. Our data show that pyrene has specific effects on chemokine synthesis, which are not restricted to mediators primarily associated with atopic diseases. Pyrene also affected cells not derived from lung tissue, which suggests a broader immunoregulatory influence for this pollutant.
Bömmel
Heike
H
Biocenter, Department of Physiological Chemistry II, 97074 Würzburg, Germany.
Haake
Markus
M
Luft
Petra
P
Horejs-Hoeck
Jutta
J
Hein
Herbert
H
Bartels
Joachim
J
Schauer
Christian
C
Pöschl
Ulrich
U
Kracht
Michael
M
Duschl
Albert
A
D000393:Air Pollutants / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D011721:Pyrenes / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001335:Vehicle Emissions
D000393:Air Pollutants; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016209:Interleukin-8; D011721:Pyrenes; D001335:Vehicle Emissions