Regeneration of Pulp-dentin Complex by Antimicrobial Peptides

LL 37是18 kDa阳离子抗微生物蛋白C-末端的最后37个氨基酸，并显示出对革兰氏阳性和阴性细菌的抗微生物活性。在可逆性牙髓炎的治疗中，清除细菌、抑制炎症、促进牙髓细胞功能是牙髓-牙本质复合体再生的必要条件。除了抗微生物活性之外，LL 37还可以影响细胞因子表达和牙髓细胞功能的活化。在本研究中，我们研究了LL 37对炎症细胞因子IL-6和IL-8的基因表达以及人牙髓细胞（HP细胞）迁移的影响。（1）炎性细胞因子表达：1. HP细胞表达P2X_7受体。LL 37和P2X_7受体激动剂Bz-ATP可阻断肽聚糖刺激的HP细胞IL-6和IL-8 mRNA水平的升高。LL 37不影响碱性磷酸酶和骨粘连蛋白的mRNA表达。因此，LL 37可能具有通过P2X_7受体抑制细胞因子表达的能力。(2)迁移：LL 37可能通过激活EGF受体和INK来诱导HP细胞迁移，这表明LL 37除了具有抗菌活性外，还具有抑制细胞因子表达和诱导牙髓细胞迁移的能力。LL 37可能在牙髓-牙本质复合体的再生中发挥作用。

LL37 is the last 37 amino acid at the C-terminus of 18 kDa cationic antimicrobial protein and shows antimicrobial activity against Gram-positive and -negative bacteria. Elimination of bacteria, inhibition of inflammation and promotion of pulp cell function are necessary for regeneration of pulp-dentin complex in the treatment of reversible pulpitis. In addition to antimicrobial activity, LL37 also may influences cytokine expression and activation of pulp cell function. In the present study, we examined the effects of LL37 on the gene expression of inflammatory cytokines, IL-6 and IL-8 and migration in human pulp cells (HP cells). (1)Expression of inflammatory cytokine expression: 1. HP cells expressed P2X_7 receptor. LL37 as well as Bz-ATP, an agonist of P2X_7 receptor abolished the increase in IL-6 and IL-8 mRNA levels in HP cells stimulated with peptidoglycan. LL37 did not influence mRNA expression of ALPase and osteonectin. Thus, LL37 may possess the ability to inhibit cytokine expression through P2X_7 receptor.(2) Migration: LL37 is suggested to induce migration of HP cells through transactivation of EGF receptor and activation of INK.These findings demonstrated that in addition to antimicrobial activity, LL37 possesses the ability to inhibit cytokine expression and induce migration of pulp cells. LL37 may play a role in regeneration of pulp-dentin complex.