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Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing

Nature Medicine volume 6, pages 1147–1153 (2000)Cite this article

Abstract

Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor with anti-microbial properties found in mucosal fluids. It is expressed during cutaneous wound healing. Impaired healing states are characterized by excessive proteolysis and often bacterial infection, leading to the hypothesis that SLPI may have a role in this process. We have generated mice null for the gene encoding SLPI (Slpi), which show impaired cutaneous wound healing with increased inflammation and elastase activity. The altered inflammatory profile involves enhanced activation of local TGF-β in Slpi-null mice. We propose that SLPI is a pivotal endogenous factor necessary for optimal wound healing.

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Figure 1: SLPI is expressed during normal wound repair.
Figure 2: Delayed wound healing in Slpi-null mice.
Figure 3: Increased inflammation in the Slpi-null wounds.
Figure 4: The absence of SLPI leads to increased wound elastase activity and reduced matrix.
Figure 5: Exogenous SLPI reverses the impaired wound healing phenotype in Slpi-null mice.
Figure 6: TGF-β activation, but not RNA, is increased in the absence of SLPI.
Figure 7: Neutralization of TGF-β accelerates healing in the Slpi-null mice.

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Acknowledgements

We thank M. Goldberg, F. Harper and D. Sim for technical assistance; S. Vogel for Mac-2 antibody; A. Nagy for the R1 ES cells; V. Campbell for ganciclovir; K. Flanders for LC I-30; and N. McCartney-Francis for review of the manuscript. G.A. was supported by a Clinician Scientist Fellowship from the Wellcome Trust, UK.

Author information

Author notes

  1. Gillian S. Ashcroft and Kejian Lei: G.A. & K.L. contributed equally to this study.

Authors and Affiliations

  1. Oral Infection and Immunity Branch, National Institute of Dental & Craniofacial Research, Building 30, 30 Convent Drive, MSC 4352

    Gillian S. Ashcroft, Kejian Lei, Wenwen Jin, Teresa Greenwell-Wild, Hollie Hale-Donze, George McGrady, Xiao-Yu Song & Sharon M. Wahl

  2. National Institutes of Health, Bethesda, 20892, Maryland, USA

    Gillian S. Ashcroft, Kejian Lei, Wenwen Jin, Teresa Greenwell-Wild, Hollie Hale-Donze, George McGrady, Xiao-Yu Song & Sharon M. Wahl

  3. Gene Targeting Facility, National Institute of Dental & Craniofacial Research, Building 30, 30 Convent Drive, MSC 4352

    Glenn Longenecker & Ashok B. Kulkarni

  4. National Institutes of Health, Bethesda , 20892, Maryland, USA

    Glenn Longenecker & Ashok B. Kulkarni

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Correspondence to Sharon M. Wahl.

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Ashcroft, G., Lei, K., Jin, W. et al. Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nat Med 6, 1147–1153 (2000). https://doi.org/10.1038/80489

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