Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432–1 Horinouchi, Hachioji, Tokyo 192–0392, Japan.
Biol Pharm Bull. 2011;34(2):295-9. doi: 10.1248/bpb.34.295.
Aberrant extracellular matrix (ECM) remodeling in sebaceous glands and pilosebaceous units in the skin is associated with scar formation under acne conditions. To investigate the involvement of Propionibacterium acnes (P. acnes), a Gram-positive anaerobic microbial species, in ECM remodeling in sebaceous glands and pilosebaceous units, we examined the effects of P. acnes culture media, formalin-fixed P. acnes, and peptidoglycan (PGN) from Gram-positive bacteria walls on the production of promatrix metalloproteinase 2 (proMMP-2)/progelatinase A in hamster sebocytes and dermal fibroblasts. When hamster sebocytes (1.8×10(5) cells) and dermal fibroblasts (1×10(5) cells) were treated with P. acnes culture media and formalin-fixed P. acnes (corresponding to 1×10(6) and 1×10(7) bacterial cells), the production of proMMP-2 was augmented. In addition, PGN (5-50 µg/ml) dose-dependently augmented the production of proMMP-2 in both cells. Furthermore, the PGN (50 µg/ml)-augmented proMMP-2 production was resulted from an increase of its transcript. In contrast, there were no changes in cell proliferative activity in either the P. acnes or PGN-treated sebocytes and dermal fibroblasts, indicating that the augmented proMMP-2 production was not due to an increase in cell numbers. Therefore, these results provide novel evidence that PGN transcriptionally up-regulates the production of proMMP-2 in hamster sebocytes and dermal fibroblasts. Given an increase in the quantity of Gram-positive bacteria, including P. acnes in acne lesions, the aberrant ECM degradation may progress in sebaceous glands and pilosebaceous units, which is associated with acne scar formation.
皮脂腺和毛囊中的细胞外基质(ECM)异常重塑与痤疮条件下的瘢痕形成有关。为了研究丙酸杆菌(P. acnes),一种革兰阳性厌氧菌,在皮脂腺和毛囊中的 ECM 重塑中的作用,我们研究了 P. acnes 培养物、甲醛固定的 P. acnes 和革兰阳性菌细胞壁的肽聚糖(PGN)对仓鼠皮脂腺细胞和真皮成纤维细胞中前基质金属蛋白酶 2(proMMP-2)/前明胶酶 A 的产生的影响。当用 P. acnes 培养物和甲醛固定的 P. acnes(分别对应于 1×10(6)和 1×10(7)个细菌细胞)处理仓鼠皮脂腺细胞(1.8×10(5)个细胞)和真皮成纤维细胞(1×10(5)个细胞)时,proMMP-2 的产生增加。此外,PGN(5-50μg/ml)剂量依赖性地增加了这两种细胞中 proMMP-2 的产生。此外,PGN(50μg/ml)-增强的 proMMP-2 产生是由于其转录物的增加。相比之下,在 P. acnes 或 PGN 处理的皮脂腺细胞和真皮成纤维细胞中,细胞增殖活性没有变化,表明增加的 proMMP-2 产生不是由于细胞数量的增加。因此,这些结果提供了新的证据表明,PGN 转录上调了仓鼠皮脂腺细胞和真皮成纤维细胞中 proMMP-2 的产生。由于痤疮病变中包括 P. acnes 在内的革兰阳性菌数量增加,皮脂腺和毛囊中的 ECM 降解可能会异常进展,这与痤疮瘢痕形成有关。