Liu Philip T, Krutzik Stephan R, Kim Jenny, Modlin Robert L
Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, USA.
J Immunol. 2005 Mar 1;174(5):2467-70. doi: 10.4049/jimmunol.174.5.2467.
A major consequence of microbial infection is the tissue injury that results from the host inflammatory response. In acne, inflammation is due in part to the ability of Propionibacterium acnes to activate TLR2. Because all-trans retinoic acid (ATRA) decreases inflammation in acne, we investigated whether it regulates TLR2 expression and function. Treatment of primary human monocytes with ATRA led to the down-regulation of TLR2 as well as its coreceptor CD14, but not TLR1 or TLR4. The ability of a TLR2/1 ligand to trigger monocyte cytokine release was inhibited by pre- and cotreatment with ATRA; however, TLR4 activation was affected by cotreatment only. ATRA also down-regulated monocyte cytokine induction by P. acnes. These data indicate that ATRA exerts an anti-inflammatory effect on monocytes via two pathways, one specifically affecting TLR2/1 and CD14 expression and one independent of TLR expression. Agents that target TLR expression and function represent a novel strategy to treat inflammation in humans.
微生物感染的一个主要后果是由宿主炎症反应导致的组织损伤。在痤疮中，炎症部分归因于痤疮丙酸杆菌激活Toll样受体2（TLR2）的能力。由于全反式维甲酸（ATRA）可减轻痤疮中的炎症，我们研究了它是否调节TLR2的表达和功能。用ATRA处理原代人单核细胞导致TLR2及其共受体CD14的下调，但不影响TLR1或TLR4。TLR2/1配体触发单核细胞细胞因子释放的能力在预处理和同时处理ATRA时均受到抑制；然而，TLR4激活仅受同时处理的影响。ATRA还下调了痤疮丙酸杆菌诱导的单核细胞细胞因子。这些数据表明，ATRA通过两条途径对单核细胞发挥抗炎作用，一条途径特异性影响TLR2/1和CD14的表达，另一条途径独立于TLR表达。靶向TLR表达和功能的药物代表了一种治疗人类炎症的新策略。
