Adsorbed soluble organics seem to be the main drivers of inflammatory responses induced by
diesel exhaust particles (
DEP). The specific compounds contributing to this process and the cellular mechanisms behind
DEP-induced
inflammation are not well known. We have assessed pro-inflammatory effects of
DEP and various soluble
DEP fractions, in human bronchial epithelial cells (BEAS-2B).
DEP increased the expression of
interleukin (IL)-6 and CXCL8. Silencing of the
aryl hydrocarbon receptor (AhR) by
siRNA or pretreatment with AhR-antagonists did not attenuate
DEP-induced
IL-6 and CXCL8 responses. However, the halogenated
aromatic hydrocarbon (HAH)-selective AhR antagonist
CH223191 caused a considerable reduction in
DEP-induced
CYP1A1 expression indicating that this response may be due to
dioxin or
dioxin-like constituents in
DEP. Knock-down of
protease activated receptor (PAR)-2 attenuated
IL-6 responses without affecting CXCL8.
Antioxidants did not affect
IL-6 expression after 4h
DEP-exposure and only partly reduced CXCL8 expression. However, after 24h exposure
antioxidant treatment partly suppressed
IL-6 protein release and completely blocked CXCL8 release. Furthermore, a
heptane-soluble (non-polar) extract of
DEP induced both
IL-6 and CXCL8 release, whereas a PBS-soluble (highly polar) extract induced only
IL-6. Thus, pro-inflammatory responses in
DEP-exposed epithelial cells appear to be the result of both
reactive oxygen species and receptor signaling, mediated through combinatorial effects between both non-polar and polar constituents adhered to the particle surface.