Kim In Sik, Lee Na Rae, Baek Seung Yeop, Kim Eun Jeong, Kim Jung Seok, Jeong Tae-Sook, Shin Dong-Ha, Park Ho-Yong, Lee Ji-Sook
Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 301‑746, Republic of Korea.
Industrial Bio‑material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305‑806, Republic of Korea.
Mol Med Rep. 2015 May;11(5):3995-4001. doi: 10.3892/mmr.2015.3225. Epub 2015 Jan 19.
Arazyme is a metalloprotease released by Aranicola proteolyticus that was shown to inhibit cytokine release in HaCaT and endothelial cells. However, the regulatory effects of arazyme in atopic dermatitis remain to be fully understood. In the present study, the anti‑inflammatory effects of arazyme in BALB/c and Nc/Nga mice induced with 2,4‑dinitrochlrobenzene (DNCB) were investigated. BALB/c mice were sensitized with DNCB and were subsequently administered arazyme for 4 weeks either orally, dorsally or orally/dorsally. Arazyme administration significantly reduced epidermal thickening and infiltration of inflammatory cells into the dermis compared with the DNCB group. However, serum immunoglobulin E (IgE) levels were not altered by arazyme treatment. Additionally, the level of secretion of interleukins (IL)‑4, ‑5 and ‑13 in the splenocytes of BALB/c mice was elevated following stimulation with concanavalin A, while the increase of IL‑4 and IL‑13 was inhibited by arazyme. Administration of arazyme (25 mg/kg in phosphate‑buffered saline) to Nc/Nga mice that had been sensitized with DNCB for 6 weeks reduced the skin severity score compared with that in the DNCB group and inhibited the histological manifestations of atopic dermatitis‑like skin lesions. In addition, the serum IgE levels were reduced in the arazyme‑treated NC/Nga mice relative to the DNCB group. Collectively, these results indicated that arazyme attenuates the development of atopic dermatitis‑like lesions via lowering the levels of IgE and inflammatory cytokines. The results of the present study will aid in the development of effective therapeutic strategies for the treatment of allergic diseases, including atopic dermatitis.
Arazyme是由蛋白水解阿拉尼菌释放的一种金属蛋白酶，已证明其能抑制HaCaT细胞和内皮细胞中的细胞因子释放。然而，Arazyme在特应性皮炎中的调节作用仍有待充分了解。在本研究中，研究了Arazyme对用2,4-二硝基氯苯（DNCB）诱导的BALB/c和Nc/Nga小鼠的抗炎作用。用DNCB使BALB/c小鼠致敏，随后分别通过口服、背部或口服/背部给予Arazyme 4周。与DNCB组相比，给予Arazyme可显著减轻表皮增厚和炎性细胞向真皮的浸润。然而，Arazyme治疗并未改变血清免疫球蛋白E（IgE）水平。此外，用伴刀豆球蛋白A刺激后，BALB/c小鼠脾细胞中白细胞介素（IL）-4、-5和-13的分泌水平升高，而Arazyme可抑制IL-4和IL-13的升高。对用DNCB致敏6周的Nc/Nga小鼠给予Arazyme（25 mg/kg溶解于磷酸盐缓冲盐水中），与DNCB组相比，皮肤严重程度评分降低，且抑制了特应性皮炎样皮肤病变的组织学表现。此外，与DNCB组相比，Arazyme治疗的NC/Nga小鼠血清IgE水平降低。总体而言，这些结果表明，Arazyme通过降低IgE和炎性细胞因子水平来减轻特应性皮炎样病变的发展。本研究结果将有助于开发治疗包括特应性皮炎在内的过敏性疾病的有效治疗策略。
