Human |[beta]|-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response

doi:doi:10.1038/icb.2008.56

Immunology and Cell Biology (2008) 86, 643–649; doi:10.1038/icb.2008.56; published online 19 August 2008

Human -defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response

Lindsey C Pingel¹, Karl G Kohlgraf¹, Christopher J Hansen¹, Christopher G Eastman¹, Deborah E Dietrich¹, Kindra K Burnell¹, Rupasree N Srikantha¹, Xiangjun Xiao¹, Myriam Bélanger², Ann Progulske-Fox², Joseph E Cavanaugh³, Janet M Guthmiller⁴, Georgia K Johnson⁵, Sophie Joly¹, Zoya B Kurago⁶, Deborah V Dawson¹ and Kim A Brogden^1,5

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

Top

Abstract

Regulatory mechanisms in mucosal secretions and tissues recognize antigens and attenuate pro-inflammatory cytokine responses. Here, we asked whether human beta -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- alpha (TNF- alpha ) 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.