Inomata Megumi, Into Takeshi, Murakami Yukitaka
Department of Oral Microbiology, Asahi University, School of Dentistry, Mizuho, Gifu, Japan.
Eur J Oral Sci. 2010 Dec;118(6):574-81. doi: 10.1111/j.1600-0722.2010.00775.x. Epub 2010 Sep 30.
Porphyromonas gingivalis is a major periodontogenic bacterium and possesses immunostimulatory components, such as lipopolysaccharides (LPS) and fimbriae. The host antimicrobial peptide, LL-37, suppresses proinflammatory responses of immune cells but its effect on human gingival fibroblasts (HGFs) is not known. In this study, we assessed the effect of LL-37 on the proinflammatory responses of HGFs stimulated with P. gingivalis cells and their components. Live P. gingivalis cells did not induce proinflammatory responses of HGFs, and LL-37 did not alter these responses. However, LL-37 was able to suppress the killed P. gingivalis cell-induced secretion of interleukin (IL)-6 and IL-8. LL-37 also suppressed the expression of IL6, IL8, and CXCL10 genes that was induced by P. gingivalis components, including phenol-water extracts, lipid A, and fimbriae, and the induction of phosphorylation of p38 and extracellular signal-regulated kinase (ERK) by P. gingivalis lipopolysaccharide (LPS). CAMP was found to be expressed in oral epithelial cells but not in HGFs, despite stimulation with P. gingivalis components. Therefore, LL-37 can exert a suppressive effect on P. gingivalis-induced proinflammatory responses of HGFs in a paracrine manner, suggesting that excess inflammatory responses to P. gingivalis in the gingival tissue are suppressed by LL-37 in vivo.
牙龈卟啉单胞菌是一种主要的牙周致病菌,具有免疫刺激成分,如脂多糖(LPS)和菌毛。宿主抗菌肽LL-37可抑制免疫细胞的促炎反应,但其对人牙龈成纤维细胞(HGFs)的影响尚不清楚。在本研究中,我们评估了LL-37对牙龈卟啉单胞菌细胞及其成分刺激的HGFs促炎反应的影响。活的牙龈卟啉单胞菌细胞不会诱导HGFs的促炎反应,LL-37也不会改变这些反应。然而,LL-37能够抑制经热灭活的牙龈卟啉单胞菌细胞诱导的白细胞介素(IL)-6和IL-8的分泌。LL-37还抑制了牙龈卟啉单胞菌成分(包括酚水提取物、脂多糖A和菌毛)诱导的IL6、IL8和CXCL10基因的表达,以及牙龈卟啉单胞菌脂多糖(LPS)诱导的p38和细胞外信号调节激酶(ERK)的磷酸化。尽管受到牙龈卟啉单胞菌成分的刺激,但发现CAMP在口腔上皮细胞中表达,而在HGFs中不表达。因此,LL-37可以以旁分泌方式对牙龈卟啉单胞菌诱导的HGFs促炎反应发挥抑制作用,这表明体内LL-37抑制了牙龈组织中对牙龈卟啉单胞菌的过度炎症反应。