title: Role of macrophage migration inhibitory factor in heat-induced apoptosis in keratinocytes.
abstract: 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°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.
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan; and.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshihisa
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan; and.|Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Mati Ur
authors.initials: MU
authors.lastname: Rehman
authors.affiliation: Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan; and shimizut@med.u-toyama.ac.jp.
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006358:Hot Temperature; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D016159:Tumor Suppressor Protein p53; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse
keywords: JNK signaling; MIF; hyperthermia; p53; skin