丁酸和丙酸对培养的人牙龈成纤维细胞的黏附、生长、细胞周期动力学及蛋白质合成的影响

Effects of butyrate and propionate on the adhesion, growth, cell cycle kinetics, and protein synthesis of cultured human gingival fibroblasts.

作者信息

Jeng J H, Chan C P, Ho Y S, Lan W H, Hsieh C C, Chang M C

机构信息

Laboratory of Dental Pharmacology & Toxicology, School of Dentistry, National Taiwan University, Taipei.

出版信息

J Periodontol. 1999 Dec;70(12):1435-42. doi: 10.1902/jop.1999.70.12.1435.

DOI:10.1902/jop.1999.70.12.1435

PMID:10632518

Abstract

BACKGROUND

Various periodontal and root canal pathogens, such as the Bacteroides species, can produce significant amounts of short chain fatty acids (SCFA). The roles of SCFA in the pathogenesis of periodontal disease are still not fully understood.

METHODS

We therefore investigated 2 main SCFA, butyrate and propionate, on the functional behavior of cultured human gingival fibroblasts (GF) such as cell growth, protein synthesis, cell adhesion capacity, and cell cycle progression.

RESULTS

Butyrate and propionate inhibited the growth of healthy (HGF) and inflamed gingival fibroblasts (IGF) in a dose dependent manner. At concentrations of 4, 8, and 16 mM, butyrate suppressed the cell growth by 11 to 58%, 16 to 60%, and 50 to 71%, respectively. The response of cultured gingival fibroblasts to SCFA showed individual differences. Morphologically, GF became larger and more flattened in appearance following exposure to butyrate (>8 mM) and propionate (>24 mM) for 5 days. Inhibitory effects of butyrate (>2 mM) and propionate (>8 mM) on the growth of GF were due possibly to their inhibition of cell-cycle progression. At concentrations of 2 and 8 mM, butyrate led to G0/G1 arrest. Elevation of the exposure concentration to 8 to 24 mM further result in G2/M phase arrest of GF. On the other hand, propionate, at concentrations ranging from 4 to 24 mM, led to G0/G1 arrest. Butyrate (>2 mM) inhibited the proline-rich protein synthesis of GF. At concentrations of 4, 8, 16, and 24 mM, butyrate inhibited the protein synthesis of HGF-1 by 42%, 43%, 51%, and 54%, respectively. In all strains of cultured GF, the suppressive effect of propionate is less than that of butyrate. At concentration range of 4 to 24 mM, propionate suppressed the protein synthesis of HGF-1 by 23 to 43%. However, both butyrate and propionate (4 to 48 mM) exerted little effects on the adhesion of GF to type I collagen within 3 hours of incubation.

CONCLUSIONS

These results suggested that SCFA released by pathogenic microorganisms can contribute to the gingival tissue dysfunction and breakdown through their actions on specific biological functions of GF.

摘要

背景

多种牙周和根管病原体，如拟杆菌属，可产生大量短链脂肪酸（SCFA）。SCFA在牙周病发病机制中的作用仍未完全明确。

方法

因此，我们研究了两种主要的SCFA，即丁酸和丙酸，对培养的人牙龈成纤维细胞（GF）功能行为的影响，如细胞生长、蛋白质合成、细胞黏附能力和细胞周期进程。

结果

丁酸和丙酸以剂量依赖方式抑制健康牙龈成纤维细胞（HGF）和炎症牙龈成纤维细胞（IGF）的生长。在4、8和16 mM浓度下，丁酸分别使细胞生长抑制11%至58%、16%至60%和50%至71%。培养的牙龈成纤维细胞对SCFA的反应存在个体差异。形态学上，在暴露于丁酸（>8 mM）和丙酸（>24 mM）5天后，GF外观变得更大且更扁平。丁酸（>2 mM）和丙酸（>8 mM）对GF生长的抑制作用可能是由于它们对细胞周期进程的抑制。在2和8 mM浓度下，丁酸导致G0/G1期阻滞。将暴露浓度提高到8至24 mM会进一步导致GF的G2/M期阻滞。另一方面，丙酸在4至24 mM浓度范围内导致G0/G1期阻滞。丁酸（>2 mM）抑制GF富含脯氨酸的蛋白质合成。在4、8、16和24 mM浓度下，丁酸分别抑制HGF-1的蛋白质合成42%、43%、51%和54%。在所有培养的GF菌株中，丙酸的抑制作用小于丁酸。在4至24 mM浓度范围内，丙酸抑制HGF-1的蛋白质合成23%至43%。然而，丁酸和丙酸（4至48 mM）在孵育3小时内对GF与I型胶原的黏附作用很小。