Effect of environmental pollutants on the production of pro-inflammatory cytokines by normal human dermal keratinocytes.
The effect of the environmental pollutants, diesel exhaust particles (DEP) and formaldehyde (FA), on the production of pro-inflammatory cytokines (interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-8) by normal human dermal keratinocytes (hKCs) was investigated. Normal hKCs were incubated with various concentrations of DEP (0.4, 0.8, 4, or 20 microg/ml) or FA (0.25, 0.5, 1, or 5 microg/ml), and cytokine production was then determined by enzyme-linked immunosorbent assay (ELISA). DEP (20 microg/ml) induced IL-1beta production without altering cell growth. The increased production of IL-1beta induced by this concentration of DEP was further enhanced by the presence of phorbol 12-myristate 13-acetate (PMA), although PMA alone did not affect the levels of IL-1beta. IL-8 production was also increased by DEP (0.4 and 0.8 microg/ml), which is consistent with the results that these concentrations of DEP increased the number of cells significantly after 72 h incubation. Although FA alone did not stimulate the production of IL-1beta or IL-8 by keratinocytes, FA (0.5 microg/ml and 5 microg/ml) significantly increased IL-8 and IL-1beta production, respectively, in cells stimulated with PMA. IL-1alpha production was not modulated by FA or DEP even in the presence of PMA. TNF-alpha was produced by unstimulated keratinocytes at barely detectable levels after 48 h incubation. Although basal levels of TNF-alpha in the culture supernatants were increased after stimulation with PMA, neither pollutant alone nor combination with PMA affected the levels of TNF-alpha. These in vitro findings suggest that environmental pollutants may act as modulating factors of cutaneous inflammation by affecting the ability of keratinocytes to release pro-inflammatory cytokines.
Ushio
H
H
Division of Environmental Health Sciences, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Nohara
K
K
Fujimaki
H
H
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004785:Environmental Pollutants / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D005557:Formaldehyde / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D001335:Vehicle Emissions / Q000633:toxicity
D016207:Cytokines; D004785:Environmental Pollutants; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D005557:Formaldehyde