title: Catecholamine stress alters neutrophil trafficking and impairs wound healing by β2-adrenergic receptor-mediated upregulation of IL-6.
abstract: Stress-induced hormones can alter the inflammatory response to tissue injury; however, the precise mechanism by which epinephrine influences inflammatory response and wound healing is not well defined. Here we demonstrate that epinephrine alters the neutrophil (polymorphonuclear leukocyte (PMN))-dependent inflammatory response to a cutaneous wound. Using noninvasive real-time imaging of genetically tagged PMNs in a murine skin wound, chronic, epinephrine-mediated stress was modeled by sustained delivery of epinephrine. Prolonged systemic exposure of epinephrine resulted in persistent PMN trafficking to the wound site via an IL-6-mediated mechanism, and this in turn impaired wound repair. Further, we demonstrate that β2-adrenergic receptor-dependent activation of proinflammatory macrophages is critical for epinephrine-mediated IL-6 production. This study expands our current understanding of stress hormone-mediated impairment of wound healing and provides an important mechanistic link to explain how epinephrine stress exacerbates inflammation via increased number and lifetime of PMNs.
authors.affiliation: Department of Biomedical Engineering, University of California at Davis, Davis, California, USA; Department of Biological Sciences, Kent State University, Kent, Ohio, USA.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Dermatology, School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: Farzam
authors.initials: F
authors.lastname: Gorouhi
authors.affiliation: Department of Dermatology, School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ramirez
authors.affiliation: School of Veterinary Medicine: Pathology, Microbiology, Immunology, University of California at Davis School of Veterinary Medicine, Davis, California, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Granick
authors.affiliation: School of Veterinary Medicine: Pathology, Microbiology, Immunology, University of California at Davis School of Veterinary Medicine, Davis, California, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Byrne
authors.affiliation: Department of Dermatology, School of Medicine, University of California at Davis, Davis, California, USA; Shriners Hospital of Northern California, Sacramento, California, USA.
authors.forename: Athena M
authors.initials: AM
authors.lastname: Soulika
authors.affiliation: Department of Biomedical Engineering, University of California at Davis, Davis, California, USA.
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
authors.affiliation: Department of Dermatology, School of Medicine, University of California at Davis, Davis, California, USA; Dermatology Section, Department of Veterans Affairs, Northern California Health Care System, Mather, California, USA. Electronic address: rrisseroff@ucdavis.edu.
authors.forename: Rivkah R
authors.initials: RR
authors.lastname: Isseroff
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004837:Epinephrine / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000293:injuries; D013312:Stress, Physiological / Q000276:immunology; D013566:Sympathomimetics / Q000276:immunology / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D018343:Receptors, Adrenergic, beta-2; D013566:Sympathomimetics; C577686:interleukin-6, mouse; D004837:Epinephrine