title: Mitogen-Activated Protein Kinase 2 Signaling Shapes Macrophage Plasticity in Aggregatibacter actinomycetemcomitans-Induced Bone Loss.
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.
authors: Department of Oral Health Sciences and the Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, USA.
authors: Bethany A
authors: BA
authors: Herbert
authors: Department of Oral Health Sciences and the Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, USA.
authors: Heidi M
authors: HM
authors: Steinkamp
authors: Institute of Biochemistry, Hannover Medical School, Hannover, Germany.
authors: Matthias
authors: M
authors: Gaestel
authors: Department of Oral Health Sciences and the Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, USA klkirk@musc.edu.|Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors: Keith L
authors: KL
authors: Kirkwood
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity*; D016301:Alveolar Bone Loss / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000378:metabolism / Q000382:microbiology; D016871:Pasteurellaceae Infections / Q000378:metabolism / Q000382:microbiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D018925:Chemokines; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D012313:RNA; D000099190:MAP-Kinase-Activated Kinase 2
keywords: Aggregatibacter actinomycetemcomitans; chemokine receptors; chemokines; mitogen-activated protein kinases; neutrophils; osteoclast