Contact with
antigen on T-cells is made via the
T-cell receptor/
CD3 complex plus CD28, resulting in the production of
cytokines including
interleukin (IL)-2,
IL-4 and
interferon (IFN)-gamma. In particular, dysregulation of IFN-gamma and
IL-4 accounts in part for organ-specific
autoimmune diseases, allergic
inflammation and other chronic inflammatory disorders. The dried above-ground parts of Schizonepeta tenuifolia Briq are used for the treatment of
common cold and skin rashes observed in allergic
dermatitis,
psoriasis and other dermatological disorders in
oriental medicine. In the present study, we investigated whether S. tenuifolia water extract (STE) may modulate systemic levels of IFN-gamma,
IL-4 and
IL-2 in anti-CD3-stimulated mice and the production of those
cytokines in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs). In addition, the effects of STE on anti-CD3-induced activation of several
transcription factors were examined.
Oral administration of STE significantly reduced the serum levels of IFN-gamma and
IL-4 from anti-CD3-treated mice but enhanced those of
IL-2. Similar patterns were demonstrated in anti-CD3-stimulated splenocytes and PBMCs in vitro. Further analysis showed that STE enhanced the nuclear translocation of nuclear factor of activated T cells (NFAT)c2 but reduced that of the nuclear factor (
NF)-kappaB. The downregulation of IFN-gamma and
IL-4 was not mediated by its effects on signal transducer and activator of transcription (STAT)4 and STAT6 activation. These results suggest that the differential regulation of STE on IFN-gamma,
IL-4 and
IL-2 may be due to its suppression of
NF-kappaB, concomitant with its enhancement of NFATc2. Further mechanistic work is required to investigate the role of STE on its modulation of anti-CD3-induced
cytokines.