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Effects of kynurenine on CD 3+ and macrophages in wound healing
Author(s) -
Salimi Elizei Sanam,
PoormasjediMeibod MaliheSadat,
Li Yunyuan,
Baradar Jalili Reza,
Ghahary Aziz
Publication year - 2015
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12252
Subject(s) - chemokine , wound healing , flow cytometry , immune system , inflammation , chemistry , microbiology and biotechnology , proinflammatory cytokine , immunology , biology
As prolongation of the inflammation phase in a healing process frequently leads to wound impairment, here we queried whether kynurenine ( K yn) 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 K yn were conducted and compared. The result of a protein microarray revealed that the expression of 12 pro‐inflammatory cytokines and chemokines was modulated in K yn‐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, CXCL 1, C ‐ C motif ligand [ CCL ] 12, CXCL 9, CCL 4, CXCL 2, and CCL 5) in response to K yn treatment. To test the anti‐inflammatory effect of K yn 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 K yn 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 CD 3+ cells and macrophages ( CD 11b+) 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 CD 3+ cells, but not CD 11b+ cells, at different time intervals examined. These findings collectively suggest that K yn, as a small molecule, can potentially be used to overcome the difficulties associated with persistency of inflammation in healing wounds.