Mitogen-Activated Protein Kinase 2 Signaling Shapes Macrophage Plasticity in Aggregatibacter actinomycetemcomitans-Induced Bone Loss

Bethany A Herbert; Heidi M Steinkamp; Matthias Gaestel; Keith L Kirkwood

doi:10.1128/IAI.00552-16

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Mitogen-Activated Protein Kinase 2 Signaling Shapes Macrophage Plasticity in Aggregatibacter actinomycetemcomitans-Induced Bone Loss

Journal article

Open access

Peer reviewed

Mitogen-Activated Protein Kinase 2 Signaling Shapes Macrophage Plasticity in Aggregatibacter actinomycetemcomitans-Induced Bone Loss

Bethany A Herbert, Heidi M Steinkamp, Matthias Gaestel and Keith L Kirkwood

Infection and immunity, Vol.85(1)

01/2017

DOI: 10.1128/IAI.00552-16

PMCID: PMC5203644

PMID: 27795356

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https://europepmc.org/articles/pmc5203644View

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Abstract

Aggregatibacter actinomycetemcomitans is associated with aggressive periodontal disease, which is characterized by inflammation-driven alveolar bone loss. A. actinomycetemcomitans activates the p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase 2 (MK2) stress pathways in macrophages that are involved in host responses. During the inflammatory process in periodontal disease, chemokines are upregulated to promote recruitment of inflammatory cells. The objective of this study was to determine the role of MK2 signaling in chemokine regulation during A. actinomycetemcomitans pathogenesis. Utilizing a murine calvarial model, Mk2 and Mk2 mice were treated with live A. actinomycetemcomitans bacteria at the midsagittal suture. MK2 positively regulated the following macrophage RNA: Emr1 (F4/80), Itgam (CD11b), Csf1r (M-CSF Receptor), Itgal (CD11a), Tnf, and Nos2 Additionally, RNA analysis revealed that MK2 signaling regulated chemokines CCL3 and CCL4 in murine calvarial tissue. Utilizing the chimeric murine air pouch model, MK2 signaling differentially regulated CCL3 and CCL4 in the hematopoietic and nonhematopoietic compartments. Bone resorption pits in calvaria, observed by micro-computed tomography, and osteoclast formation were decreased in Mk2 mice compared to Mk2 mice after A. actinomycetemcomitans treatment. In conclusion, these data suggest that MK2 in macrophages contributes to regulation of chemokine signaling during A. actinomycetemcomitans-induced inflammation and bone loss.

Aggregatibacter actinomycetemcomitans - pathogenicity

Alveolar Bone Loss - metabolism

Alveolar Bone Loss - microbiology

Alveolar Bone Loss - physiopathology

Animals

Cells, Cultured

Chemokines - metabolism

Inflammation - metabolism

Inflammation - microbiology

Inflammation - physiopathology

Intracellular Signaling Peptides and Proteins - metabolism

Macrophages - metabolism

Macrophages - microbiology

Macrophages - physiology

Male

Mice

Mice, Inbred C57BL

Osteoclasts - metabolism

Osteoclasts - microbiology

Pasteurellaceae Infections - metabolism

Pasteurellaceae Infections - microbiology

Protein-Serine-Threonine Kinases - metabolism

RNA - metabolism

Signal Transduction - physiology

Details

Title: Subtitle: Mitogen-Activated Protein Kinase 2 Signaling Shapes Macrophage Plasticity in Aggregatibacter actinomycetemcomitans-Induced Bone Loss
Creators: Bethany A Herbert - Medical University of South Carolina
Heidi M Steinkamp - Medical University of South Carolina
Matthias Gaestel - Medizinische Hochschule Hannover
Keith L Kirkwood - Medical University of South Carolina
Resource Type: Journal article
Publication Details: Infection and immunity, Vol.85(1)
DOI: 10.1128/IAI.00552-16
PMID: 27795356
PMCID: PMC5203644
NLM abbreviation: Infect Immun
ISSN: 0019-9567
eISSN: 1098-5522
Grant note: F30 DE024368 / NIDCR NIH HHS
Language: English
Date published: 01/2017
Academic Unit: Pediatric Dentistry
Record Identifier: 9984367739202771

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