1. ¹Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA, USA
2. ²Center for Molecular Biology and Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA
3. ³Department of Biostatistics, College of Public Health, The University of Iowa, Iowa City, IA, USA
4. ⁴Department of Periodontics, School of Dentistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
5. ⁵Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA, USA
6. ⁶Department of Oral & Maxillofacial Pathology, Radiology and Medicine, New York University College of Dentistry, New York, NY, USA

Correspondence: Professor KA Brogden, Department of Periodontics, The University of Iowa, Dows Institute for Dental Research, 801 Newton Road, Iowa City, IA 52242, USA. E-mail: kim-brogden@uiowa.edu

Received 15 April 2008; Revised 3 July 2008; Accepted 8 July 2008; Published online 19 August 2008.

Abstract

Regulatory mechanisms in mucosal secretions and tissues recognize antigens and attenuate pro-inflammatory cytokine responses. Here, we asked whether human -defensin 3 (HBD3) serves as an upstream suppressor of cytokine signaling that binds and attenuates pro-inflammatory cytokine responses to recombinant hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis strain 381. We found that HBD3 binds to immobilized rHagB and produces a significantly higher resonance unit signal in surface plasmon resonance spectroscopic analysis, than HBD2 and HBD1 that are used as control defensins. Furthermore, we found that HBD3 significantly attenuates (P<0.05) the interleukin (IL)-6, IL-10, granulocyte macrophage colony stimulating factor (GM-CSF) and tumor-necrosis factor- (TNF-) responses induced by rHagB in human myeloid dendritic cell culture supernatants and the extracellular signal-regulated kinases (ERK 1/2) response in human myeloid dendritic cell lysates. Thus, HBD3 binds rHagB and this interaction may be an important initial step to attenuate a pro-inflammatory cytokine response and an ERK 1/2 response.