Attenuation of butyric acid-induced T cell apoptosis by human gingival fibroblast

(1)丁酸对F41-G和Ca9-22细胞有剂量依赖性抑制作用，但与T细胞、B细胞和单核细胞相比，其抑制作用不明显。(2)用酶联免疫吸附试验检测牙周成纤维细胞培养上清液中IL-1α、IL-1β、IL-6、IL-8、IL-11、肿瘤坏死因子α和转化生长因子β的表达时，丁酸可显著增加细胞产生IL-6、IL-8和IL-11。在Gin1、F41-G和H.牙髓细胞中加入5 mM丁酸时，这些细胞因子的水平最高。这些水平是1,500至1,900 pg/ml(IL-6)，约4,000至5,000 pg/ml(IL-8)，约900至1,100 pg/ml(IL-11)。(3)将Jurkat细胞与F41G或Gin 1细胞与部分挽救的丁酸或Fas诱导的Jurkat细胞凋亡共同培养，表明成纤维细胞释放的一种可溶性因子在防止T细胞凋亡方面发挥作用。(4)IL-6和IL-8以剂量依赖的方式轻微刺激丁酸或Fas诱导的Jurkat细胞的凋亡。IL-11显著抑制Jurkat细胞的凋亡，并呈剂量依赖性。这些结果提示，丁酸诱导的成纤维细胞产生的炎症细胞因子IL-6、IL-8和IL-11的综合作用，可能与抑制牙周成纤维细胞T细胞的凋亡有关。(5)细胞与细胞的直接相互作用表明，附着在牙周成纤维细胞上的Jurkat T细胞的凋亡被显著挽救。加入丁酸后，成纤维细胞表面CD47、CD44和CD58的表达增加，提示这些细胞表面分子的增加可能与丁酸抑制T细胞凋亡有关。

(1) Although butyric acid exhibited a dose-dependent inhibition in F41-G and Ca 9-22 cells, their effect was not prominent compared to the data with T-, B- and monocytic cells. Furthermore, the results of DNA fragmentation assay indicated that butyric acid did not induced apoptosis in human gingival fibroblasts (Gin 1, F41G and H.pulp).(2) When the culture supernatants of gingival fibroblasts were assayed for IL-1α, IL-1β, IL-6, IL-8, IL-11, TNF α and TGF β by use of ELISA kits, butyric acid significautly increased IL-6, IL-8 and IL-11 production. Maximum levels of these cytokines were noted by the addition of 5 mM butyric acid in Gin 1, F41-G and H.pulp cells. These levels were 1,500 to 1,900 pg/ml (IL-6), ca.4,000 to 5,000 pg/ml (IL-8), and ca.900 to 1,100 pg/ml (IL-11).(3) Co-culturing Jurkat cells with F41G or Gin 1 cells using intercup partially rescued butyric acid- or Fas-induced Jurkat cell apoptosis, suggest a role for a soluble factor released from fibroblasts in preventing T cell-apoptosis.(4) IL-6 and IL-8 slightly stimulated butyric acid- or Fas-induced Jurkat cell apoptosis in a dose-dependent manner, in contrast, IL-11 significantly suppressed these Jurkat cell apoptosis dose-dependently. These results suggest that the sum of their effects of the inflammatory cytokines such as IL-6, IL-8 and IL-11, produced in fibroblast by the addition of butyric acid, are concernted in the attenuation of T cell apoptosis by gingival fibroblast.(5) Furthemore, the direct cell-cell interaction indicated that the apoptosis of Jurkat T cells attached on the gingival fibroblasts was significantly rescued. CD47, CD44 and CD58 expression on the fibroblasts was increased by the addition of butyric acid, suggest that the increase of these cell surface molecule was concerned with the suppression of T cell apoptosis induced by butyric acid.