Adrenergic signaling in human oral keratinocytes and wound repair.
Catecholamines are present in saliva, but their influence on oral epithelium is not understood. Because psychological stress increases salivary catecholamines and impairs oral mucosal wound healing, we sought to determine if epithelial adrenergic signaling could link these two findings. We found that cultured human oral keratinocytes (HOK) express the α(2B)- and β(2)-adrenergic receptors (ARs). Exposure of HOK to either epinephrine or the β-AR agonist, isoproterenol, reduced migratory speed and decreased in vitro scratch wound healing. Incubation with the β-AR antagonist timolol reversed the catecholamine-induced effects, indicating that the observed response is mediated by β-AR. Epinephrine treatment decreased phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2 and p38; these decreases were also reversed with timolol. Cultured HOK express enzymes of the epinephrine synthetic pathway, and generate epinephrine. These findings demonstrate that stress-induced elevations of salivary catecholamines signal through MAPK pathways, and result in impaired oral keratinocyte migration required for healing.
Department of Dermatology, University of California, Davis, School of Medicine, TB 192, One Shields Ave., Davis, CA 95616, USA.
P
P
Steenhuis
R E
RE
Huntley
Z
Z
Gurenko
L
L
Yin
B A
BA
Dale
N
N
Fazel
R R
RR
Isseroff
D002465:Cell Movement; D002478:Cells, Cultured; D004837:Epinephrine / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D010766:Phosphorylation; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018343:Receptors, Adrenergic, beta-2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004837:Epinephrine