First Author | Yoshihisa Y | Year | 2016 |
Journal | FASEB J | Volume | 30 |
Issue | 11 | Pages | 3870-3877 |
PubMed ID | 27528627 | Mgi Jnum | J:239689 |
Mgi Id | MGI:5829505 | Doi | 10.1096/fj.201600408RR |
Citation | Yoshihisa Y, et al. (2016) Role of macrophage migration inhibitory factor in heat-induced apoptosis in keratinocytes. FASEB J 30(11):3870-3877 |
abstractText | In human skin, keratinocytes are constantly challenged by adverse influences, such as hot and cold temperatures; however, the effects of heat on apoptosis induction in keratinocytes are not well understood. Macrophage migration inhibitory factor (MIF) is a potent cytokine that overcomes p53 function by suppressing its transcriptional activity. Here, we evaluated the effects of MIF on hyperthermia (HT)-induced apoptosis in MIF-deficient [knockout (KO)] and MIF-transgenic (Tg) mouse keratinocytes. Cells were exposed to HT at 44 degrees C, and increased apoptosis was observed in MIF-KO and wild-type (WT) cells compared with MIF-Tg cells. To determine the mechanism, MIF-mediated changes in the cellular p53 level and its effects on p53-dependent death signaling (Bax and p21) and JNK signaling (p-JNK, JNK, p-Bad, and Bad) were investigated. MIF-Tg cells exhibited substantially decreased levels of p53 after HT treatment compared with WT and MIF-KO cells. In addition, HT treatment caused decreased expression of p-JNK and p-Bad in MIF-Tg cells; however, no such changes were observed in MIF-KO and WT cells. These results showed that the activation of JNK (p-JNK and p-Bad) and p53 may be involved in HT-induced apoptosis in keratinocytes and that enhanced endogenous MIF expression suppressed apoptosis.-Yoshihisa, Y., Rehman, M. U., Kondo, T., Shimizu, T. Role of macrophage migration inhibitory factor in heat-induced apoptosis in keratinocytes. |