title: Severe multiple organ injury in HSF1 knockout mice induced by lipopolysaccharide is associated with an increase in neutrophil infiltration and surface expression of adhesion molecules.
abstract: We have reported previously that HSF1 is essential in protection against the lethal systemic inflammation induced by LPS. However, the mechanism by which HSF1 protects against LPS-induced systemic inflammation remains unknown. In this study, HSF1(-/-) mice were subjected to endotoxemia by a bolus injection of LPS (10 mg/kg, i.p.). The serum levels of LDH, BUN, and transaminase (ALT and AST) were measured. PMN infiltration in lung, liver, and kidney tissues after endotoxemia was observed with immunohistochemistry. Comparing with the WT control, LPS administration induced more severe multiple organ dysfunction and lower survival rates in the HSF1(-/-) mice. Moreover, PMN infiltration into lungs, liver, and kidneys in HSF1(-/-) mice was more than that in the WT mice. The augmented tissue PMN infiltration in HSF1(-/-) mice was associated with their enhanced adhesive properties to endothelium in vivo. In addition, HSF1(-/-) caused greater surface expression of PSGL-1 and CD11b on the PMN surface after LPS treatment. These findings suggested that HSF1 alleviated LPS-induced multiple organ injury in mice by suppressing the surface expression of adhesion molecules on PMNs and subsequent infiltration of PMNs in tissues.
authors: Department of Pathophysiology, Xiangya School of Medicine, Changsha, Hunan, People’s Republic of China.
authors: Shuhua
authors: S
authors: Chen
authors: Xiaoxia
authors: X
authors: Zuo
authors: Mingshi
authors: M
authors: Yang
authors: Hongwei
authors: H
authors: Lu
authors: Nian
authors: N
authors: Wang
authors: Kangkai
authors: K
authors: Wang
authors: Zizhi
authors: Z
authors: Tu
authors: Guangwen
authors: G
authors: Chen
authors: Meidong
authors: M
authors: Liu
authors: Ke
authors: K
authors: Liu
authors: Xianzhong
authors: X
authors: Xiao
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D000076249:Heat Shock Transcription Factors; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D009102:Multiple Organ Failure / Q000517:prevention & control*; D020556:Neutrophil Infiltration / Q000187:drug effects*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D014157:Transcription Factors