Defensin DEFB103 bidirectionally regulates chemokine and cytokine responses to a pro-inflammatory stimulus

Lauren E Harvey; Karl G Kohlgraf; Leslie A Mehalick; Monica Raina; Erica N Recker; Saumya Radhakrishnan; Samiksha Avinash Prasad; Robinson Vidva; Ann Progulske-Fox; Joseph E Cavanaugh; Shireen Vali; Kim A Brogden

doi:10.1038/srep01232

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Defensin DEFB103 bidirectionally regulates chemokine and cytokine responses to a pro-inflammatory stimulus

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Defensin DEFB103 bidirectionally regulates chemokine and cytokine responses to a pro-inflammatory stimulus

Lauren E Harvey, Karl G Kohlgraf, Leslie A Mehalick, Monica Raina, Erica N Recker, Saumya Radhakrishnan, Samiksha Avinash Prasad, Robinson Vidva, Ann Progulske-Fox, Joseph E Cavanaugh, …

Scientific reports, Vol.3(1), pp.1232-1232

2013

DOI: 10.1038/srep01232

PMCID: PMC3565171

PMID: 23390582

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Abstract

Human β defensin DEFB103 acts as both a stimulant and an attenuator of chemokine and cytokine responses: a dichotomy that is not entirely understood. Our predicted results using an in silico simulation model of dendritic cells and our observed results in human myeloid dendritic cells, show that DEFB103 significantly (p < 0.05) enhanced 6 responses, attenuated 7 responses, and both enhanced/attenuated the CXCL1 and TNF responses to Porphyromonas gingivalis hemagglutinin B (HagB). In murine JAWSII dendritic cells, DEFB103 significantly attenuated, yet rarely enhanced, the Cxcl2, Il6, and Csf3 responses to HagB; and in C57/BL6 mice, DEFB103 significantly enhanced, yet rarely attenuated, the Cxcl1, Csf1, and Csf3 responses. Thus, DEFB103 influences pro-inflammatory activities with the concentration of DEFB103 and order of timing of DEFB103 exposure to dendritic cells, with respect to microbial antigen exposure to cells, being paramount in orchestrating the onset, magnitude, and composition of the chemokine and cytokine response.

Tumor Necrosis Factor-alpha - metabolism

Cytokines - metabolism

Humans

Mice, Inbred C57BL

Macrophage Colony-Stimulating Factor - metabolism

Adhesins, Bacterial - toxicity

Animals

Porphyromonas gingivalis - metabolism

beta-Defensins - pharmacology

Dendritic Cells - drug effects

Lectins - toxicity

Chemokines - metabolism

Mice

Chemokine CXCL1 - metabolism

Dendritic Cells - metabolism

Details

Title: Subtitle: Defensin DEFB103 bidirectionally regulates chemokine and cytokine responses to a pro-inflammatory stimulus
Creators: Lauren E Harvey - Dows Institute for Dental Research or Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Karl G Kohlgraf
Leslie A Mehalick
Monica Raina
Erica N Recker
Saumya Radhakrishnan
Samiksha Avinash Prasad
Robinson Vidva
Ann Progulske-Fox
Joseph E Cavanaugh
Shireen Vali
Kim A Brogden
Resource Type: Journal article
Publication Details: Scientific reports, Vol.3(1), pp.1232-1232
DOI: 10.1038/srep01232
PMID: 23390582
PMCID: PMC3565171
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: R01 DE014390 / NIDCR NIH HHS
Language: English
Date published: 2013
Academic Unit: Statistics and Actuarial Science; Preventive and Community Dentistry; Biostatistics; Injury Prevention Research Center; Dental Research; Periodontics
Record Identifier: 9983985715502771

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