title: Hyperthermia suppresses the cytotoxicity of NK cells via down-regulation of perforin/granzyme B expression.
abstract: Hyperthermia, which is used as an adjunctive therapy for cancer, is known to modulate the activity of natural killer (NK) cells in vitro, but its effect in vivo is unclear. In the present study, we used a whole body hyperthermia (WBH) device heated by infrared rays to evaluate the effect of WBH on mice models. We demonstrate here that wild type C57BL/6J mice exposed to 42 degrees C for 60min had reduced NK cell cytolytic activity against YAC-1 target cells as determined by cytolytic assay. This result was confirmed using Rag-2 knockout mice, which possess functional NK but not cytolytic T or NK-T cells. Moreover, WBH decreased the mRNA expression of perforin and granzyme B in spleens of mice. But the expression of TNF cytokines (Fas ligand and TRAIL) was unchanged. These data suggest that the suppression of NK cell activity induced by WBH could be mediated through the perforin/granzyme pathway.
authors.affiliation: Department of Molecular Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Koga
authors.forename: Hideki
authors.initials: H
authors.lastname: Harada
authors.forename: Tea Seow
authors.initials: TS
authors.lastname: Shi
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Suico
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shuto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005334:Fever / Q000503:physiopathology*; D053804:Granzymes; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; C499308:Rag2 protein, mouse; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases