Antiapoptotic role of p38 mitogen activated protein kinase in Jurkat T cells and normal human T lymphocytes treated with 8-methoxypsoralen and ultraviolet-A radiation

Abstract

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.

Systems Kinomics Demonstrates Congo Basin Monkeypox Virus Infection Selectively Modulates Host Cell Signaling Responses as Compared to West African Monkeypox Virus

“…Although the activation of p38 MAPK signaling is classically related to stress responses and activation of cell death (51), there is increasing evidence that under certain circumstances p38 MAPK can enhance cell survival. Indeed, p38 MAPK activation has been demonstrated to enhance cell survival responses to DNA damage (52,53 (55). Although these investigations have provided important information regarding modulation of host immunity by Congo Basin MPXV, the integration of systems kinomics has provided pertinent functional information regarding the differential host response to Congo Basin MPXV and the less-virulent West African MPXV clade and identified potential host targets for therapeutic intervention.…”

In vivo and in vitro demonstration of herb-drug interference in human breast cancer cells treated with tamoxifen and trastuzumab

“…It has been found that down-regulation of FOXO1A results in the nuclear export of p27(Kip1) and that reactivation of FOXO1A also restores the growth-inhibitory effects of trastuzumab on SK-BR-3 cells. 34 Moreover, P38 MAPK has been shown to play an important role in cell growth regulation and to have antiapoptotic ability not only in T lymphocytes 35 and smooth muscle cells 36 but also in cancer cells. 37 Our results demonstrate that SWT reverses trastuzumabinduced cytotoxicity in SK-BR-3 and BT-474 cells, partly through activation of AKT signaling and suppression of p27(Kip1) function and partly through activation of the P38 MAPK pathway.…”

Redox Regulation of Cell Survival

“…A recent study showed that the SAPK pathways can also induce apoptosis through the death-receptor pathway (280,282). Conversely, JNK or p38 MAPK activation has been reported to have an antiapoptotic effect in malignant B and T lymphocytes, respectively (41,191). The bifunctional role of the SAPK pathways in cell-fate decision may be dependent on different cell types and stimuli.…”