title: Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation.
abstract: Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice.
authors.affiliation: Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luana Graziella
authors.initials: LG
authors.lastname: Bandeira
authors.affiliation: Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Beatriz Salari
authors.initials: BS
authors.lastname: Bortolot
authors.affiliation: Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Matheus Jorand
authors.initials: MJ
authors.lastname: Cecatto
authors.affiliation: Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Andréa
authors.initials: A
authors.lastname: Monte-Alto-Costa
authors.affiliation: Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Romana-Souza
mesh_terms: D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008676:Metanephrine / Q000097:blood; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D062326:Re-Epithelialization; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D014364:Tryptophan / Q000097:blood / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014409:Tumor Necrosis Factor-alpha; D008676:Metanephrine; D014364:Tryptophan; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt