Abstract
To investigate the mechanism of the glucocorticoids-
induced augmentation of skin response, we
have recently reported the modulatory effect of glucocorticoids
on the regulation of cytokines production
in keratinocytes stimulated with various
chemicals in vitro through both NF-κB and AP-1
activation. Further to clarify the mechanism in the
glucocorticoids-induced augmentation of cytokines
production from keratinocytes, we examined
the effect of glucocorticoids to keratinocytes
without chemical stimulation.
Glucocorticoids 10–4 M inhibited the production
of IL-1α from Pam 212 cells. However, lower concentration
(10–8–10–10 M) of glucocorticoids significantly
enhanced the production of IL-1α by Pam
212 cells at both the protein and mRNA levels. In
contrast, glucocorticoids had no effect on the
production of either TNF-α, IL-6, nor GM-CSF by
Pam 212 cells cultured for 6 h. Electrophoretic
mobility shift assays (EMSA) revealed that
10–10–10–12 M glucocorticoids induced the NF-κB
activation in Pam 212 cells, however, augmented
AP-1 activation by 10–8–10–10 M of glucocorticoids
was observed in Pam 212 cells.
Furthermore, pyrrolidine dithiocarbamate (PDTC)
partially inhibited the IL-1α production and completely
inhibited NF-κB expression by Pam 212
cells. On the other hand, MAP-kinase inhibitors
(PD98059, SB202190) completely abrogated not
only AP-1 activation but the low concentration
glucocorticoids-induced IL-1α production.
These data indicated that lower concentration of
glucocorticoids induced the augmentation of IL-1α
production from keratinocytes mediated through
the AP-1 pathway and partially through NF-κB
pathway.
