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Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein

In English

Författare

  • G Canny
  • E Cario
  • Andreas Lennartsson
  • Urban Gullberg
  • C Brennan
  • O Levy
  • SP Colgan

Summary, in English

Epithelial cells of many mucosal organs have adapted to coexist with microbes and microbial products. In general, most studies suggest that epithelial cells benefit from interactions with commensal microorganisms present at the lumenal surface. However, potentially injurious molecules found in this microenvironment also have the capacity to elicit local inflammatory responses and even systemic disease. We have recently demonstrated that epithelia cells express the anti-infective molecule bactericidal/permeability-increasing protein (BPI). Here, we extend these findings to examine molecular mechanisms of intestinal epithelial cell (IEC) BPI expression and function. Initial experiments revealed a variance of BPI mRNA and protein expression among various IEC lines. Studies of BPI promoter expression in IECs identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. To assess the functional significance of this protein, we generated an IEC line stably transfected with full-length BPI. We demonstrated that, whereas epithelia express markedly less BPI protein than neutrophils, epithelial BPI contributes significantly to bacterial killing and attenuating bacterial-elicted proinflammatory signals. Additional studies in murine tissue ex vivo revealed that BPI is diffusely expressed along the crypt-villous axis and that epithelial BPI levels decrease along the length of the intestine. Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces.

Publiceringsår

2006

Språk

Engelska

Sidor

557-567

Publikation/Tidskrift/Serie

American Journal of Physiology: Gastrointestinal and Liver Physiology

Volym

290

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

American Physiological Society

Ämne

  • Physiology

Nyckelord

  • mucosa
  • inflammation
  • intestine
  • transcription
  • infection

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1522-1547