Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium

David R. Hill, Sean P. Kessler, Hyunjin K. Rho, Mary Cowman, Carol A. De La Motte

Research output: Contribution to journalArticle

Abstract

Hyaluronan (HA) is a glycosaminoglycan polymer found in the extracellular matrix of virtually all mammalian tissues. Recent work has suggested a role for small, fragmented HA polymers in initiating innate defense responses in immune cells, endothelium, and epidermis through interaction with innate molecular pattern recognition receptors, such as TLR4. Despite these advances, little is known regarding the effect of fragmented HA at the intestinal epithelium, where numerous pattern recognition receptors act as sentinels of an innate defense response that maintains epithelial barrier integrity in the presence of abundant and diverse microbial challenges. Here we report that HA fragments promote expression of the innate antimicrobial peptide human β-defensin 2 (HβD2) in intestinal epithelial cells. Treatment of HT-29 colonic epithelial cells withHAfragment preparations resulted in time- and dose-dependent up-regulated expression of HβD2 protein in a fragment size-specific manner, with 35-kDa HA fragment preparations emerging as the most potent inducers of intracellular HβD2. Furthermore, oral administration of specific-sized HA fragments promotes the expression of an HβD2 ortholog in the colonic epithelium of both wild-type and CD44-deficient mice but not in TLR4-deficient mice. Together, our observations suggest that a highly size-specific, TLR4-dependent, innate defense response to fragmented HA contributes to intestinal epithelium barrier defense through the induction of intracellular HβD2 protein.

Original languageEnglish (US)
Pages (from-to)30610-30624
Number of pages15
JournalJournal of Biological Chemistry
Volume287
Issue number36
DOIs
StatePublished - Aug 31 2012

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Defensins
Hyaluronic Acid
Intestinal Mucosa
Pattern Recognition Receptors
Polymers
Epithelial Cells
Glycosaminoglycans
Epidermis
Endothelium
Extracellular Matrix
Oral Administration
Proteins
Epithelium
Tissue
Peptides

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium. / Hill, David R.; Kessler, Sean P.; Rho, Hyunjin K.; Cowman, Mary; De La Motte, Carol A.

In: Journal of Biological Chemistry, Vol. 287, No. 36, 31.08.2012, p. 30610-30624.

Research output: Contribution to journalArticle

Hill, David R. ; Kessler, Sean P. ; Rho, Hyunjin K. ; Cowman, Mary ; De La Motte, Carol A. / Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 36. pp. 30610-30624.
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