異位性皮膚炎(atopic dermatitis, AD)為一種皮膚慢性發炎的過敏性疾病，歐洲塵螨(Dermatophagoides pteronyssinu, Der p)為台灣主要過敏原，可誘發發炎反應進而產生異位性皮膚炎的症狀，皮膚出現大量細胞凋亡(apoptosis)的現象。臨床上常以益生菌作為過敏性疾病的輔助療法，本實驗室過去發現加氏乳酸桿菌(Lactobacillus gasseri, LG)可改善異位性皮膚炎的症狀，且乳酸菌去氫酶蛋白(Lactobacillus dehydrogenase proteins, LDHs)可能是有效的抗敏成份，由於其作用機轉尚未清楚，故本研究目的主要探討乳酸菌去氫酶蛋白是否具治療異位性皮膚炎的療效及作用機轉。因此為了探討乳酸菌去氫酶蛋白在異位性皮膚炎的治療效果，我們先以歐洲塵螨經皮致敏的方式，促進小鼠產生異位性皮膚炎症狀。接著本研究透過該動物模式探討LDHs的治療效果，結果發現LDHs可改善小鼠皮膚皺褶、減少皮屑和經皮水分散失以及減緩塵螨引起的發炎反應，包括減少免疫球蛋白E(Immunoglobulin E, IgE)及胸腺淋巴生成素(thymic stromal lymphopoietin, TSLP)的濃度、嗜酸性球(eosinophis)與蘭格罕細胞(Langerhans cells, LCs)的浸潤。此外，LDHs透過抑制M30和凋亡蛋白酶(casspase 3)的表現，減少塵螨引起的角質細胞凋亡化(apoptosis)。最後以人類角質細胞HaCaT細胞，探討LDHs是否透過提升具抗發炎作用之氧化體增殖酶活化受體g(peroxisome proliferator-activated receptor gamma, PPARg而改善塵螨引起的細胞凋亡。結果顯示塵螨會誘使HaCaT細胞減少PPARg並增加caspase 3的表現，而預先給予LDHs時可改善角質細胞因塵螨而凋亡的現象；但LDHs合併PPARg抑制劑給予細胞後則無法改善此現象。綜合本研究結果得知，LDHs可以促進調控PPARg而改善角質細胞凋亡化，亦即乳酸菌去氫酶蛋白可能為治療該疾病的新劑型，同時也提供治療異位性皮膚炎的新方向。

Atopic dermatitis (AD) is an allergic disease mediated by keratinocyte apoptosis and chronic relapsing inflammation of the skin. In our previous study, we found that Lactobacillus gasseri (LG) could alleviate the symptoms of AD. Furthermore, Lactobacillus dehydrogenase proteins (LDHs) might be the most potential ingredient to modulate the allergic inflammation, but the underlying mechanism is unknown. Therefore, in this study, we aimed to investigate the mechanism of how LDHs attenuated AD. We established Dermatophagoides pteronyssinus (Der p)-induced AD mouse model through epicutaneous challenging (EC) to examine the treatment effect of LDHs. The results showed that LDHs could improve the physiological and pathological function of AD lesion skin. It could also diminish TH2-mediated inflammation including extenuating total and Der p-specific IgE levels, amounts of eosinophils and Langerhans cells (LCs) infiltrated into skin, and TSLP expression in epidermis. Moreover, LDHs could decrease Der p induced keratinocyte apoptosis through inhibiting M30 and caspase-3 level. Next, we used human keratinocyte cell line (HaCaT) to investigate whether LDHs could induce an anti-inflammatory protein, peroxisome proliferator-activated receptor gamma (PPARg and contribute to attenuating keratinocyte apoptosis. The results showed that Der p down-regulated PPARg expression but up-regulated caspase-3 expression in HaCaT cell. LDHs pre-treatment could inhibit Der p induced HaCaT cells apoptosis. However, LDHs combined with PPARg antagonist pre-treatment could not reverse this situation. Accordingly, we have demonstrated that LDHs could attenuate Der p-induced keratinocyte apoptosis through up-regulating PPARg expression and diminishing allergic inflammation. Our finding provides a new therapeutic option for AD patients.

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