Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients.
Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients.
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DOI：
10.1038/jid.2012.111
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发表时间：
2012-09
影响因子：
6.5
通讯作者：
Thiboutot, Diane M.
中科院分区：
文献类型：
--
作者：
Dispenza, Melanie C.;Wolpert, Ellen B.;Gilliland, Kathryn L.;Dai, Jenny P.;Cong, Zhaoyuan;Nelson, Amanda M.;Thiboutot, Diane M.
类维生素A用于治疗炎症性皮肤病和恶性肿瘤，但缺乏表征这些药物在人体内作用的研究。异维甲酸是全反式维甲酸的前药，可诱导痤疮的长期缓解;然而，其完整的作用机制尚不清楚。我们假设异维甲酸通过使对痤疮丙酸杆菌的先天免疫反应正常化来诱导痤疮的缓解。与正常受试者相比，痤疮患者的外周血单核细胞表达显著更高水平的TLR-2，并且在痤疮丙酸杆菌刺激后表现出显著更大的TLR-2表达诱导。用异维甲酸治疗患者显著降低单核细胞TLR-2表达，并在治疗一周后降低随后对痤疮丙酸杆菌的炎性细胞因子反应。这种作用在停止治疗后持续6个月，表明TLR-2调节可能参与对异维甲酸的持久治疗反应。这项研究表明，异维A酸发挥免疫调节作用的患者，揭示了其长期影响痤疮的潜在机制。单核细胞上TLR-2表达的调节在以TLR-2失调为特征的其他炎性疾病中具有重要意义。
Retinoids are used in the treatment of inflammatory skin diseases and malignancies, but studies characterizing the in vivo actions of these drugs in humans are lacking. Isotretinoin is a pro-drug for all-trans retinoic acid that can induce long-term remissions of acne; however, its complete mechanism of action is unknown. We hypothesized that isotretinoin induces remission of acne by normalizing the innate immune response to the commensal bacterium P. acnes. Compared to normal subjects, peripheral blood monocytes from acne patients expressed significantly higher levels of TLR-2 and exhibited significantly greater induction of TLR-2 expression following P. acnes stimulation. Treatment of patients with isotretinoin significantly decreased monocyte TLR-2 expression and subsequent inflammatory cytokine response to P. acnes by one week of therapy. This effect was sustained six months following cessation of therapy, indicating that TLR-2 modulation may be involved in the durable therapeutic response to isotretinoin. This study demonstrates that isotretinoin exerts immunomodulatory effects in patients and sheds light on a potential mechanism for its long-term effects in acne. The modulation of TLR-2 expression on monocytes has important implications in other inflammatory disorders characterized by TLR-2 dysregulation.
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DOI：
10.4049/jimmunol.181.4.2277
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Xiao S;Jin H;Korn T;Liu SM;Oukka M;Lim B;Kuchroo VK
通讯作者：
Kuchroo VK
影响因子：
30.3
作者：
Montoya D;Cruz D;Teles RM;Lee DJ;Ochoa MT;Krutzik SR;Chun R;Schenk M;Zhang X;Ferguson BG;Burdick AE;Sarno EN;Rea TH;Hewison M;Adams JS;Cheng G;Modlin RL
通讯作者：
Modlin RL
DOI：
10.1038/jid.2010.351
发表时间：
2011-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.1
作者：
Kane, MA;Chen, N;Napoli, JL
通讯作者：
Napoli, JL
影响因子：
4.4
作者：
Liu, PT;Krutzik, SR;Modlin, RL
通讯作者：
Modlin, RL