title: Effects of kynurenine on CD3+ and macrophages in wound healing.
abstract: As prolongation of the inflammation phase in a healing process frequently leads to wound impairment, here we queried whether kynurenine (Kyn) could modulate this phase of wound healing. To address this, a protein microarray, quantitative polymerase chain reaction (qPCR), flow cytometry for immune cells and immune cell proliferation in the presence and absence of Kyn were conducted and compared. The result of a protein microarray revealed that the expression of 12 pro-inflammatory cytokines and chemokines was modulated in Kyn-treated mouse splenocytes as compared with those of control. These findings were then evaluated by conducting a qPCR for the gene expression of these factors and showed a significant reduction in the gene expression of majority of these cytokines and chemokines (interleukin [IL]-2, IL-17, C-X-C motif chemokine ligand [CXCL] 10, CXCL1, C-C motif ligand [CCL] 12, CXCL9, CCL4, CXCL2, and CCL5) in response to Kyn treatment. To test the anti-inflammatory effect of Kyn in an animal model, dorsal surface wounds were generated in a mouse model and wounds received daily topical application of either nothing (control), dermal cream (second control), or Kyn cream using uninjured skin tissue as another control. The wounded tissues were harvested on days 3, 6, and 10 postwounding. As anticipated, the results of fluorescence-activated cell sorting analysis revealed that upon wounding, the number of total infiltrated CD3+ cells and macrophages (CD11b+) significantly increased on day 3, peaked on day 6, and reduced on day 10 post-wounding. Interestingly, as compared with those of uninjured and dermal cream alone-treated wounds, Kyn treatment significantly reduced the number of infiltrated CD3+ cells, but not CD11b+ cells, at different time intervals examined. These findings collectively suggest that Kyn, as a small molecule, can potentially be used to overcome the difficulties associated with persistency of inflammation in healing wounds.
authors.affiliation: BC Professional Fire Fighters' Burn and Wound Healing Research Laboratory, Division of Plastic Surgery, Department of Surgery, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Sanam
authors.initials: S
authors.lastname: Salimi Elizei
authors.forename: Malihe-Sadat
authors.initials: MS
authors.lastname: Poormasjedi-Meibod
authors.forename: Yunyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Reza
authors.initials: R
authors.lastname: Baradar Jalili
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007249:Inflammation; D007737:Kynurenine / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016133:Polymerase Chain Reaction; D040081:Protein Array Analysis; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D003879:Dermatologic Agents; D007737:Kynurenine