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Infection and Immunity, June 1999, p. 2740-2745, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Production of beta -Defensin Antimicrobial Peptides by the Oral Mucosa and Salivary Glands

Michael Mathews,1 Hong Peng Jia,2 Janet M. Guthmiller,1 Garrett Losh,3 Scott Graham,3 Georgia K. Johnson,1 Brian F. Tack,4 and Paul B. McCray Jr.2,*

Department of Periodontics and Dows Institute for Dental Research1 and Departments of Microbiology,4 Otolaryngology,3 and Pediatrics,2 University of Iowa Colleges of Medicine and Dentistry, Iowa City, Iowa

Received 24 November 1998/Returned for modification 8 January 1999/Accepted 3 March 1999

beta -Defensins are cationic peptides with broad-spectrum antimicrobial activity that are produced by epithelia at mucosal surfaces. Two human beta -defensins, HBD-1 and HBD-2, were discovered in 1995 and 1997, respectively. However, little is known about the expression of HBD-1 or HBD-2 in tissues of the oral cavity and whether these proteins are secreted. In this study, we characterized the expression of HBD-1 and HBD-2 mRNAs within the major salivary glands, tongue, gingiva, and buccal mucosa and detected beta -defensin peptides in salivary secretions. Defensin mRNA expression was quantitated by RNase protection assays. HBD-1 mRNA expression was detected in the gingiva, parotid gland, buccal mucosa, and tongue. Expression of HBD-2 mRNA was detected only in the gingival mucosa and was most abundant in tissues with associated inflammation. To test whether beta -defensin expression was inducible, gingival keratinocyte cell cultures were treated with interleukin-1beta (IL-1beta ) or bacterial lipopolysaccharide (LPS) for 24 h. HBD-2 expression increased ~16-fold with IL-1beta treatment and ~5-fold in the presence of LPS. Western immunoblotting, liquid chromatography, and mass spectrometry were used to identify the HBD-1 and HBD-2 peptides in human saliva. Human beta -defensins are expressed in oral tissues, and the proteins are secreted in saliva; HBD-1 expression was constitutive, while HBD-2 expression was induced by IL-1beta and LPS. Human beta -defensins may play an important role in the innate defenses against oral microorganisms.

* Corresponding author. Mailing address: Department of Pediatrics, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, IA 52242. Phone: (319) 356-4866. Fax: (319) 356-7171. E-mail: paul-mccray{at}uiowa.edu.

Infection and Immunity, June 1999, p. 2740-2745, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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