Department of R & D, Microbial Institute for Fermentation Industry, Sunchang, South Korea.
Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, South Korea.
Biomed Pharmacother. 2020 Sep;129:110488. doi: 10.1016/j.biopha.2020.110488. Epub 2020 Jul 6.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with intestinal microflora. Since specific probiotics may have better efficacy for AD, we determined the efficacy of Pediococcus acidilactici SRCM102024 (PA) for treating AD in HaCaT cells and NC/Nga mice and explored the mechanism of action. AD-like pathology was induced in HaCaT cells and the dorsal skin of Nc/Nga mice by local exposure to 2,4-dinitrochlorobenzene (DNCB). In AD-lesion induced mice, PA in low-, medium- and high-dosages (5 × 10E6, 5 × 10E7 and 5 × 10E8 CFU/kg bw, respectively) and dexamethasone (3 mg/kg bw, positive-control) were orally administered for 5 weeks. The clinical AD severity, serum immunoglobulin E (IgE) and TNF-α, gene expressions of interleukin (IL)-4, IL-13, and TNF-α and gut microflora were measured. PA treatment (100-300 CFU/mL) dose-dependently increased cell survival in DNCB-induced HACAT cells. PA reduced the relative mRNA expression of PAR-2, TNF-α, IL-4 and IL-13 in the cells. In dorsal skin of Nc/Nga mice applied with DNCB, PA dose-dependently attenuated erythema, hemorrhage, edema, excoriation, dryness and scratching behavior and PA-H improved the clinical symptoms similar to the positive-control. PA-M and PA-H treatment significantly prevented the disturbance of the dorsal skin tissues and decreased the inflammatory cellular infiltrate of mast cells, compared to the control. PA dose-dependently reduced serum IgE and TNF-α concentrations and the mRNA expression of TNF-α, IL-4, and IL-13 in dorsal skin. In gut microflora, relative counts of Lactobacillales, Butyricicoccus and Ruminococcus were decreased in the AD-control compared to the positive-control and the PA-M and PA-H prevented their decrease. However, the positive-control increased serum AST and ALT activities, indicating liver damage as an adverse effect. In conclusion, oral treatment of PA (human equivalent 1 × 10E9-1 × 10E10) relieved the AD symptoms by dose-dependently preventing over-activation of the immune response. Oral PA intake may be a safe and effective alternative therapy for AD.
特应性皮炎（AD）是一种与肠道微生物群相关的慢性炎症性皮肤病。由于特定的益生菌可能对 AD 有更好的疗效，我们确定了嗜酸乳球菌 SRCM102024（PA）治疗 HaCaT 细胞和 NC/Nga 小鼠 AD 的疗效，并探讨了其作用机制。通过局部暴露于 2,4-二硝基氯苯（DNCB）在 HaCaT 细胞和 Nc/Nga 小鼠的背部皮肤中诱导 AD 样病变。在 AD 病变诱导的小鼠中，以低、中、高剂量（分别为 5×10E6、5×10E7 和 5×10E8 CFU/kg bw）和地塞米松（阳性对照，3mg/kg bw）口服给予 PA 治疗 5 周。测量临床 AD 严重程度、血清免疫球蛋白 E（IgE）和 TNF-α、白细胞介素（IL）-4、IL-13 和 TNF-α的基因表达以及肠道微生物群。PA 治疗（100-300 CFU/mL）剂量依赖性地增加 DNCB 诱导的 HACAT 细胞的细胞存活率。PA 降低了细胞中 PAR-2、TNF-α、IL-4 和 IL-13 的相对 mRNA 表达。在应用 DNCB 的 Nc/Nga 小鼠背部皮肤中，PA 剂量依赖性地减轻了红斑、出血、水肿、抓挠、干燥和抓挠行为，PA-H 改善了类似于阳性对照的临床症状。与对照组相比，PA-M 和 PA-H 治疗显著防止了背部皮肤组织的紊乱，并减少了肥大细胞的炎症细胞浸润。PA 剂量依赖性地降低了血清 IgE 和 TNF-α浓度以及背部皮肤中 TNF-α、IL-4 和 IL-13 的 mRNA 表达。在肠道微生物群中，与阳性对照相比，AD 对照组中乳杆菌目、丁酸球菌和真杆菌的相对计数减少，而 PA-M 和 PA-H 则阻止了它们的减少。然而，阳性对照增加了血清 AST 和 ALT 活性，表明肝脏损伤是一种不良反应。总之，PA（人类等效 1×10E9-1×10E10）的口服治疗通过剂量依赖性地防止免疫反应过度激活，缓解了 AD 症状。口服 PA 摄入可能是 AD 的一种安全有效的替代治疗方法。
