Human beta-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response.
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.
Pingel
Lindsey C
LC
Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
Kohlgraf
Karl G
KG
Hansen
Christopher J
CJ
Eastman
Christopher G
CG
Dietrich
Deborah E
DE
Burnell
Kindra K
KK
Srikantha
Rupasree N
RN
Xiao
Xiangjun
X
Bélanger
Myriam
M
Progulske-Fox
Ann
A
Cavanaugh
Joseph E
JE
Guthmiller
Janet M
JM
Johnson
Georgia K
GK
Joly
Sophie
S
Kurago
Zoya B
ZB
Dawson
Deborah V
DV
Brogden
Kim A
KA
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*
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