Accelerated wound healing phenotype in Interleukin 12/23 deficient mice

<p>Abstract</p> <p>Background</p> <p>The concept that a strong inflammatory response involving the full complement of cytokines and other mediators is critical for unimpaired healing has been challenged by wound healing studies using transgenic and knockout (KO) mice. T...

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Main Authors: Matias Marie AT, Saunus Jodi M, Ivanovski Saso, Walsh Laurence J, Farah Camile S
Format: Article
Language:English
Published: BMC 2011-12-01
Series:Journal of Inflammation
Subjects:
Online Access:http://www.journal-inflammation.com/content/8/1/39
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author Matias Marie AT
Saunus Jodi M
Ivanovski Saso
Walsh Laurence J
Farah Camile S
author_facet Matias Marie AT
Saunus Jodi M
Ivanovski Saso
Walsh Laurence J
Farah Camile S
author_sort Matias Marie AT
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The concept that a strong inflammatory response involving the full complement of cytokines and other mediators is critical for unimpaired healing has been challenged by wound healing studies using transgenic and knockout (KO) mice. The present study explored the effect of abrogation of the p40 subunit, which is shared by the pro-inflammatory cytokines interleukin (IL)-12 and IL-23, on wound closure of excisional oral mucosal wounds.</p> <p>Methods</p> <p>Double IL-12 and IL-23 KO mice and C57BL ⁄ 6J wildtype mice were wounded on the dorsal surface of the tongue using a 2 mm biopsy punch. The degree of epithelialization was examined histologically. At specific timepoints wounds were examined for cellular and molecular markers for inflammation and angiogenesis using 1) immunohistochemistry; 2) analysis of RNA expression; and 3) flow cytometric analysis.</p> <p>Results</p> <p>Compared to wild type controls, KO mice displayed enhanced healing, which was driven by a greater influx of neutrophils and macrophages during the early stages of wound healing, and increased induction of messenger RNA (mRNA) for endothelial derived neutrophil attractant (ENA78) chemokine and macrophage inflammatory protein-2 alpha (MIP-2α). Increased mRNA for monocyte-attracting chemokines including monocyte chemoattractant protein (MCP)-1 and MCP-3 was seen from day 1, together with higher levels of IL-1β and IL-6 within 24 hours after wounding. In addition, mRNA for vascular endothelial growth factor (VEGF)-A was upregulated in KO mice within 2 hours after injury, and higher expression of this mediator was confirmed by immunohistochemistry.</p> <p>Conclusion</p> <p>Overall, the accelerated oral mucosal wound healing seen in IL-12/IL-23p40 KO compared to wildtype mice was associated with the early establishment of an inflammatory response and vascularization.</p>
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spelling doaj.art-3c886bf584704a46bda079b330e9e6592022-12-21T19:59:09ZengBMCJournal of Inflammation1476-92552011-12-01813910.1186/1476-9255-8-39Accelerated wound healing phenotype in Interleukin 12/23 deficient miceMatias Marie ATSaunus Jodi MIvanovski SasoWalsh Laurence JFarah Camile S<p>Abstract</p> <p>Background</p> <p>The concept that a strong inflammatory response involving the full complement of cytokines and other mediators is critical for unimpaired healing has been challenged by wound healing studies using transgenic and knockout (KO) mice. The present study explored the effect of abrogation of the p40 subunit, which is shared by the pro-inflammatory cytokines interleukin (IL)-12 and IL-23, on wound closure of excisional oral mucosal wounds.</p> <p>Methods</p> <p>Double IL-12 and IL-23 KO mice and C57BL ⁄ 6J wildtype mice were wounded on the dorsal surface of the tongue using a 2 mm biopsy punch. The degree of epithelialization was examined histologically. At specific timepoints wounds were examined for cellular and molecular markers for inflammation and angiogenesis using 1) immunohistochemistry; 2) analysis of RNA expression; and 3) flow cytometric analysis.</p> <p>Results</p> <p>Compared to wild type controls, KO mice displayed enhanced healing, which was driven by a greater influx of neutrophils and macrophages during the early stages of wound healing, and increased induction of messenger RNA (mRNA) for endothelial derived neutrophil attractant (ENA78) chemokine and macrophage inflammatory protein-2 alpha (MIP-2α). Increased mRNA for monocyte-attracting chemokines including monocyte chemoattractant protein (MCP)-1 and MCP-3 was seen from day 1, together with higher levels of IL-1β and IL-6 within 24 hours after wounding. In addition, mRNA for vascular endothelial growth factor (VEGF)-A was upregulated in KO mice within 2 hours after injury, and higher expression of this mediator was confirmed by immunohistochemistry.</p> <p>Conclusion</p> <p>Overall, the accelerated oral mucosal wound healing seen in IL-12/IL-23p40 KO compared to wildtype mice was associated with the early establishment of an inflammatory response and vascularization.</p>http://www.journal-inflammation.com/content/8/1/39Wound healingInterleukin-12Interleukin-23p40InflammationAngiogenesis
spellingShingle Matias Marie AT
Saunus Jodi M
Ivanovski Saso
Walsh Laurence J
Farah Camile S
Accelerated wound healing phenotype in Interleukin 12/23 deficient mice
Journal of Inflammation
Wound healing
Interleukin-12
Interleukin-23
p40
Inflammation
Angiogenesis
title Accelerated wound healing phenotype in Interleukin 12/23 deficient mice
title_full Accelerated wound healing phenotype in Interleukin 12/23 deficient mice
title_fullStr Accelerated wound healing phenotype in Interleukin 12/23 deficient mice
title_full_unstemmed Accelerated wound healing phenotype in Interleukin 12/23 deficient mice
title_short Accelerated wound healing phenotype in Interleukin 12/23 deficient mice
title_sort accelerated wound healing phenotype in interleukin 12 23 deficient mice
topic Wound healing
Interleukin-12
Interleukin-23
p40
Inflammation
Angiogenesis
url http://www.journal-inflammation.com/content/8/1/39
work_keys_str_mv AT matiasmarieat acceleratedwoundhealingphenotypeininterleukin1223deficientmice
AT saunusjodim acceleratedwoundhealingphenotypeininterleukin1223deficientmice
AT ivanovskisaso acceleratedwoundhealingphenotypeininterleukin1223deficientmice
AT walshlaurencej acceleratedwoundhealingphenotypeininterleukin1223deficientmice
AT farahcamiles acceleratedwoundhealingphenotypeininterleukin1223deficientmice