title: Low-grade inflammatory polarization of monocytes impairs wound healing.
abstract: Impaired wound healing often accompanies low-grade inflammatory conditions, during which circulating levels of subclinical super-low-dose endotoxin may persist. Low-grade inflammatory monocyte polarization may occur during chronic inflammation and deter effective wound repair. However, little is understood about the potential mechanisms of monocyte polarization by sustained insult of subclinical super-low-dose endotoxin. We observed that super-low-dose endotoxin preferentially programmes a low-grade inflammatory monocyte state in vitro and in vivo, as represented by the elevated population of CD11b(+) Ly6C(high) monocytes and sustained expression of CCR5. Mechanistically, super-low-dose endotoxin caused cellular stress, altered lysosome function and increased the transcription factor IRF5. TUDCA, a potent inhibitor of cellular stress, effectively blocked monocyte polarization and improved wound healing in mice injected with super-low-dose endotoxin. Our data revealed the polarization of low-grade inflammatory monocytes by sustained endotoxin challenge, its underlying mechanisms and a potential intervention strategy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Ruoxi
authors.initials: R
authors.lastname: Yuan
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Diao
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Liwu
authors.identifier: http://orcid.org/0000-0001-8870-5299
authors.initials: L
authors.lastname: Li
mesh_terms: D016764:Cell Polarity / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology / Q000502:physiology*
chemical_list: D014157:Transcription Factors
keywords: IRF5; cellular stress; innate immunity; low-grade inflammation; monocytes; wound healing