title: Human beta-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response.
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.
authors: Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors: Lindsey C
authors: LC
authors: Pingel
authors: Karl G
authors: KG
authors: Kohlgraf
authors: Christopher J
authors: CJ
authors: Hansen
authors: Christopher G
authors: CG
authors: Eastman
authors: Deborah E
authors: DE
authors: Dietrich
authors: Kindra K
authors: KK
authors: Burnell
authors: Rupasree N
authors: RN
authors: Srikantha
authors: Xiangjun
authors: X
authors: Xiao
authors: Myriam
authors: M
authors: Bélanger
authors: Ann
authors: A
authors: Progulske-Fox
authors: Joseph E
authors: JE
authors: Cavanaugh
authors: Janet M
authors: JM
authors: Guthmiller
authors: Georgia K
authors: GK
authors: Johnson
authors: Sophie
authors: S
authors: Joly
authors: Zoya B
authors: ZB
authors: Kurago
authors: Deborah V
authors: DV
authors: Dawson
authors: Kim A
authors: KA
authors: Brogden
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases; D006801:Humans; D007113:Immunity, Innate; D037102:Lectins / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System; D016966:Porphyromonas gingivalis / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance; D023083:beta-Defensins / Q000276:immunology / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D016207:Cytokines; C422950:DEFB103A protein, human; C098582:HagB protein, Porphyromonas gingivalis; D037102:Lectins; D011994:Recombinant Proteins; D023083:beta-Defensins; D048049:Extracellular Signal-Regulated MAP Kinases