Article
MicroRNA-155 aggravates the inflammatory response in ischemia-reperfusion injury following free tissue transfer via modulation of integrin expression and inflammatory cell recruitment
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Authors
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Steffen Eisenhardt
- Uniklinik Freiburg, Plastische und Handchirurgie, Freiburg
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Jakob Weiss
- Uniklinik Freiburg, Plastische und Handchirurgie, Freiburg
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Martin Moser
- Uniklinik Freiburg, Kardiologie und Angiologie, Freiburg
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Jan Thiele
- Uniklinik Freiburg, Plastische und Handchirurgie, Freiburg
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Christoph Bode
- Uniklinik Freiburg, Kardiologie und Angiologie, Freiburg
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Sebastian Grundmann
- Uniklinik Freiburg, Kardiologie und Angiologie, Freiburg
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Björn Stark
- Uniklinik Freiburg, Plastische und Handchirurgie, Freiburg
| Published: | April 26, 2013 |
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Outline
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Introduction: Ischemia-reperfusion injury (IRI) can lead to tissue injury and transplant failure in free flap surgery, macroreplantation and composite tissue allotransplantation in reconstructive microsurgery surgery. Previous work has identified a role for microRNA-155 (miR-155) in the modulation of the immune response. We hypothesized that miR155 contributes to the inflammatory response in IRI.
Material and methods: Expression levels of miR-155 were analysed by real time stem loop PCR of human striated muscle tissue after free flap surgery and IRI. Values were correlated with expression levels of markers of inflammation, angiogenesis and apoptosis, as well as SOCS-1, a direct target of miR-155. Leukocyte infiltration was analyzed by immunohistology.
The functional consequences of miR-155 in IRI were evaluated by an intravital imaging model of IRI in the cremasteric muscle of miR-155 knockout (-/-) mice compared to wildtype mice (wt). Rolling and adhesion of leukocytes in post capillary venules were monitored as parameters of inflammation; leukocyte transmigration was assessed by immunohistology. For a mechanistical analysis we evaluated the influence of miR-155 over-expression on CD11b expression in THP-1 monocytes.
Results: miR-155 expression in human striated muscle tissue is increased after IRI, significantly correlating with the increased expression of markers for inflammation (TNF-α), angiogenesis (CD105) and apoptosis (Caspase3), which is corresponding to the infiltration of inflammatory cells. Consequently, SOCS-1 is down-regulated. The intravital analysis of IRI in mice reveals attenuated rolling and adhesion of leukocytes reperfusion injury in miR-155 -/- mice compared to wt-mice.
The immunohistological analysis of murine cremasteric tissue shows significantly less infiltration of inflammatory cells in the miR-155 -/- mice compared to wt-mice. MiR-155 over-expression leads to an increase in surface-expression of CD11b.
Conclusion: Our results confirm a modulating role of miR-155 in the pathogenesis of IRI. MiR-155 aggravates the inflammatory response, leukocyte infiltration and tissue damage, partly by mediating an increased expression of leukocyte adhesion molecules. Our data suggest that miR-155 is a potential target for the treatment or prevention of IRI in various clinical settings.
