title: HSF-1 is involved in attenuating the release of inflammatory cytokines induced by LPS through regulating autophagy.
abstract: Autophagy plays a protective role in endotoxemic mice. Heat shock factor 1 (HSF-1) also plays a crucial protective role in endotoxemic mice by decreasing inflammatory cytokines. The purpose of this study was to determine whether HSF-1 is involved in attenuating the release of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated mice and peritoneal macrophages (PMs) through regulating autophagy activity. Autophagosome formation in HSF-1(+/+) and HSF-1(-/-) mice and PMs stimulated by LPS was examined by Western blotting and immunofluorescence. Lipopolysaccharide-induced autophagy and inflammatory cytokines were examined in HSF-1(+/+) and HSF-1(-/-) PMs treated with 3-methyladenine (3-MA) or rapamycin. Results showed that LPS-induced autophagy was elevated transiently at 12 h but declined at 24 h in the livers and lungs of mice. Higher levels of inflammatory cytokines and lower autophagy activity were detected in HSF-1(-/-) mice and PMs compared with HSF-1(+/+) mice and PMs. Interestingly, LPS-induced release of inflammatory cytokines did not further increase in HSF-1(-/-) PMs treated with 3-MA but aggravated in HSF-1(+/+) PMs. Lipopolysaccharide-induced autophagy did not decrease in HSF-1(-/-) PMs treated with 3-MA but decreased in HSF-1 PMs(+/+). Taken together, our results suggested that HSF-1 attenuated the release of inflammatory cytokines induced by LPS by regulating autophagy activity.
authors.affiliation: *Department of Pathophysiology, Xiangya School of Medicine, Central South University, Hunan; and †Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Tong
authors.forename: Bimei
authors.initials: B
authors.lastname: Jiang
authors.forename: Lingli
authors.initials: L
authors.lastname: Zhang
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Li
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Lu
authors.forename: Yongming
authors.initials: Y
authors.lastname: Yao
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D020123:Sirolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D008070:Lipopolysaccharides; D014157:Transcription Factors; C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus