A combination of
8-methoxypsoralen and ultraviolet-A radiation (320-400 nm) (PUVA) is used for the treatment of T cell-mediated disorders, including
chronic graft-versus-host disease, autoimmune disorders, and
cutaneous T-cell lymphomas. The mechanisms of action of this
therapy, referred to as extracorporeal
phototherapy, have not been fully elucidated. PUVA is known to induce apoptosis in T lymphocytes collected by
apheresis, however no information is available concerning the underlying signaling pathways which are activated by PUVA. In this study, we found that PUVA treatment of Jurkat cells and human T lymphocytes up-regulates the
p38 MAPK pathway but not the p42/44 MAPK or the SAPK/JNK signaling networks. The use of a pharmacological inhibitor selective for the
p38 MAPK pathway,
SB203580, allowed us to demonstrate that this network exerts an antiapoptotic effect in PUVA-treated Jurkat cells and T lymphocytes from healthy donors. Moreover, the effect of
SB203580 was not due to a down-regulation of the Akt survival pathway which was not activated in response to PUVA. These results may suggest that
p38 MAPK-dependent signaling is very important for the regulation of survival genes after exposure to PUVA. Since the
therapeutic effect of PUVA seems to depend, at least in part, on apoptosis, further studies on the apoptosis signaling networks activated by this treatment might lead to the use of signal transduction modulators in combination with PUVA, to increase the efficacy of this form of
therapy.