Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands.
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 approximately 16-fold with IL-1beta treatment and approximately 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.
Mathews
M
M
Department of Periodontics and Dows Institute for Dental Research, University of Iowa Colleges of Medicine and Dentistry, Iowa City, Iowa, USA.
Jia
H P
HP
Guthmiller
J M
JM
Losh
G
G
Graham
S
S
Johnson
G K
GK
Tack
B F
BF
McCray
P B
PB
D016475:3T3 Cells; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D002478:Cells, Cultured; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D023082:Defensins; D019075:Electrophoresis, Capillary; D005786:Gene Expression Regulation; D005881:Gingiva / Q000166:cytology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D013058:Mass Spectrometry; D051379:Mice; D009061:Mouth Mucosa / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012469:Salivary Glands / Q000378:metabolism*; D023083:beta-Defensins
D000890:Anti-Infective Agents; C406407:DEFB1 protein, human; C106641:DEFB4A protein, human; D023082:Defensins; D011506:Proteins; D023083:beta-Defensins