1. Academic Validation
  2. Determination of the optimal concentration and duration of C5aR antagonist application in an inflammatory model of human dental pulp cells

Determination of the optimal concentration and duration of C5aR antagonist application in an inflammatory model of human dental pulp cells

  • FEBS Open Bio. 2023 Feb 2. doi: 10.1002/2211-5463.13571.
Junlong Hu 1 Xiaohan Tan 2 Xiaoling Wei 3 Weiping Hu 2 Li Gao 4 Xiaofang Cao 5 Huiying Yang 6 Zhuling Jiang 7 Ning Li 8 Li Teng # 1 Mingyue Liu # 9
Affiliations

Affiliations

  • 1 Department of Craniomaxillofacial Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 33 Ba-Da-Chu Road, Shi Jing Shan District, Beijing, 100144, P.R. China.
  • 2 Department of Prosthodontics, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086.
  • 3 Hainan Dental Hospital No.50, Youyi Road, Longhua District, Haikou, Hainan, 570105, P.R. China.
  • 4 Department of Oral and Maxillofacial Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, P.R. China.
  • 5 Department of Endodontics, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, P.R. China.
  • 6 Department of stomatology, Qiqihar Eye & ENT Hospital, Qiqihar, Heilongjiang, 161000, P.R. China.
  • 7 Department of Oral Implantology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, P.R. China.
  • 8 Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, P.R. China.
  • 9 Department of Prosthodontics, the Second Affiliated Hospital of Harbin Medical University& The Key Laboratory of Myocardial Ischemia Ministry of Education, Harbin, No. 246, Xuefu Road, Harbin, Heilongjiang, 150086, P.R. China.
  • # Contributed equally.
Abstract

Deep tooth decay approaching the pulp may develop into pulpitis; to prevent this, pulp cells need to balance the rapid immune response to avoid rapid swelling of the pulp. Current treatment of deep decay that approaches the pulp involves the application of drugs that induce low-level inflammation in the dental pulp to promote its repair, but this treatment is sometimes insufficient. However, the unsuccessful treatment often resulted in pulpitis. The C5a-C5aR is the initial stage of the immune cascade response. Blocking the binding of C5a-C5aR can slow the immune response in the narrow pulp cavity so that dental pulp cells have enough time to proliferate, migrate, and differentiate. In this study, we compared lipoteichoic acid (LTA) and lipopolysaccharides (LPS) at different concentrations and time points and used the C5aR antagonist W54011 to block the C5a-C5aR axis. The blocking effect was detected by analyzing the expression of C5a, C5aR, interleukin (IL)-6, and Toll-like Receptor 2 and 4 (TLR-2, 4). Next, we determined the optimal concentration and duration of LTA and LPS treatment in combination with W54011. Based on our results, we selected 1.0 μg/mL LPS treatment for 48 h to generate an inflammatory model of human dental pulp cells. We then regrouped the cells and conducted expression analyses to monitor the expression of C5a, C5aR, IL-6, and TLR-4 at the protein and mRNA levels. LPS stimulation for 48 h and treatment with W54011 for 48 h effectively inhibited inflammation and did not affect C5a expression. This study provides a basis for follow-up studies of W54011 in dental pulp cells.

Keywords

C5aR; C5aR antagonist W54011; Dental pulp cells; Interleukin-6; Lipopolysaccharides; tooth decay.

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