Herbert Bethany A, Steinkamp Heidi M, Gaestel Matthias, Kirkwood Keith L
Department of Oral Health Sciences and the Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, USA.
Institute of Biochemistry, Hannover Medical School, Hannover, Germany.
Infect Immun. 2016 Dec 29;85(1). doi: 10.1128/IAI.00552-16. Print 2017 Jan.
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.
伴放线聚集杆菌与侵袭性牙周病相关，侵袭性牙周病的特征是炎症驱动的牙槽骨丧失。伴放线聚集杆菌激活巨噬细胞中的p38丝裂原活化蛋白激酶（MAPK）和MAPK活化蛋白激酶2（MK2）应激途径，这些途径参与宿主反应。在牙周病的炎症过程中，趋化因子上调以促进炎症细胞的募集。本研究的目的是确定MK2信号在伴放线聚集杆菌致病过程中趋化因子调节中的作用。利用小鼠颅骨模型，在矢状缝处用活的伴放线聚集杆菌处理Mk2和Mk2小鼠。MK2正向调节以下巨噬细胞RNA：Emr1（F4/80）、Itgam（CD11b）、Csf1r（M-CSF受体）、Itgal（CD11a）、Tnf和Nos2。此外，RNA分析显示MK2信号调节小鼠颅骨组织中的趋化因子CCL3和CCL4。利用嵌合小鼠气袋模型，MK2信号在造血和非造血区室中对CCL3和CCL4进行差异调节。与伴放线聚集杆菌处理后的Mk2小鼠相比，Mk2小鼠颅骨中的骨吸收凹坑和破骨细胞形成减少。总之，这些数据表明巨噬细胞中的MK2在伴放线聚集杆菌诱导的炎症和骨质流失过程中有助于趋化因子信号的调节。
