Aberrant mucosal wound repair in the absence of secretory leukocyte protease inhibitor

Nikola Angelov; Niki Moutsopoulos; Moon-Jin Jeong; Salvador Nares; Gillian Ashcroft; Sharon M. Wahl

doi:10.1160/TH03-07-0446

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(02): 288-297
DOI: 10.1160/TH03-07-0446

Theme Issue Article

Schattauer GmbH

Aberrant mucosal wound repair in the absence of secretory leukocyte protease inhibitor

Nikola Angelov^*

¹Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA

,

Niki Moutsopoulos^*

¹Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA

,

Moon-Jin Jeong

²Current address: Department of Oral Histology, College of Dentistry, Chosun University, Gwang-ju, Korea

,

Salvador Nares

¹Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA

,

Gillian Ashcroft

³Current address: School of Biological Sciences, University of Manchester, Manchester, England

,

Sharon M. Wahl

¹Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA

› Author Affiliations

Abstract

Summary

Secretory leukocyte protease inhibitor (SLPI) is a cationic serine protease inhibitor with anti-microbial and anti-inflammatory properties found in large quantities in mucosal fluids, including saliva. SLPI is expressed during cutaneous wound healing, however, its role in oral wound repair is unknown. We have used a novel approach involving a murine buccal mucosal acute wound model to investigate the role of SLPI in oral healing. In parallel to the observed cutaneous healing phenotype, an absence of SLPI results in markedly impaired oral wound healing associated with increased inflammation and raised elastase activity. Moreover, matrix deposition was decreased, while MMP activity was enhanced in the oral SLPI null wounds suggesting deregulated proteolysis. Intriguingly, regardless of genotype, reduced collagen deposition was observed in oral compared to dermal wounds, associated with reduced TGF-β expression and decreased fibroblast collagen expression in vitro. We propose that SLPI is a pivotal endogenous factor necessary for optimal tissue repair including intra-oral wound healing. In addition, our model provides a unique opportunity to delineate the cellular and molecular mechanisms underlying the differences between dermal scarring and oral scar-free healing.

Keywords

Wound healing - oral - mucosa - cutaneous - inflammation - SLPI

Full Text

References

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