Investigation of the differential potentials of TLR agonists to elicit uveitis in mice
Investigation of the differential potentials of TLR agonists to elicit uveitis in mice
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DOI：
10.1189/jlb.0511249
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发表时间：
2011-12-01
影响因子：
5.5
通讯作者：
Rosenzweig, Holly L.
中科院分区：
文献类型：
--
作者：
Allensworth, Jordan J.;Planck, Stephen R.;Rosenzweig, Holly L.
tlr对宿主防御和先天免疫至关重要。新出现的证据也支持tlr在许多慢性炎症性疾病中的作用，包括被称为葡萄膜炎的炎症性眼病。内毒素激活TLR4诱导标准小鼠葡萄膜炎模型。额外tlr的激活如何影响前葡萄膜炎的发病和/或严重程度尚未被研究。我们试图阐明tlr （TLR1/2、TLR2/6、TLR3、TLR4、TLR5、TLR7/8和TLR9）在小鼠中引发葡萄膜炎的潜力。直接刺激的虹膜/纤毛体外植体显示炎症细胞因子tnf - α、IL-6、IP-10/CXCL10、MCP-1和KC的产生显著增加，而ifn - γ、IL-10、IL-12p40、IL-12p70、IL-17、IL-1 β、IL-4或RANTES的产生相对较少。尽管存在一些差异，如TLR3激活后产生更多的IP-10，但TLR激动剂的细胞因子反应谱是相似的。眼内注射TLR激动剂增加了白细胞与虹膜血管内皮的相互作用，导致趋化进入虹膜组织。通过ivt视频显微镜和组织学评估白细胞反应，揭示了TLR激动剂在滚动、粘附、虹膜浸润和体液浸润细胞的时间和数量以及体内细胞因子水平方面的定量差异。我们的数据证明了眼睛对多种微生物产物的反应性，这些微生物产物激活了TLR，并揭示了体内各种TLR激动剂之间相对细胞反应的差异。j . Leukoc。生物学杂志。90:1159-1166；2011.
TLRs are critical for host defense and innate immunity. Emerging evidence also supports a role for TLRs in many chronic inflammatory diseases, including inflammatory eye disease, known as uveitis. The activation of TLR4 by endotoxin induces a standard model of murine uveitis. How activation of additional TLRs influences the onset and/or severity of anterior uveitis has not been examined. We sought to elucidate the potential of TLRs (TLR1/2, TLR2/6, TLR3, TLR4, TLR5, TLR7/8, and TLR9) to trigger uveitis in mice. Directly stimulated iris/ciliary body explants demonstrated a marked increase in production of inflammatory cytokines TNF-alpha, IL-6, IP-10/CXCL10, MCP-1, and KC with relatively little production of IFN-gamma, IL-10, IL-12p40, IL-12p70, IL-17, IL-1 beta, IL-4, or RANTES. The cytokine-response profiles were comparable amongst the TLR agonists, albeit some differences were noted, such as greater IP-10 production following TLR3 activation. Intra-ocular injection of TLR agonists increased leukocyte interactions with the endothelium of the iris vasculature and resulted in chemotaxis into the iris tissue. Assessment of leukocytic responses by ivt videomicroscopy and histology revealed quantitative differences amongst responses to the TLR agonists with respect to the timing and numbers of rolling, adhering, iris-infiltrating, and aqueous humor-infiltrating cells, along with cytokine levels in vivo. Our data demonstrate the eye's responsiveness to a diverse array of microbial products, which activates TLRs, and reveal differences in relative cellular response among the various TLR agonists in vivo. J. Leukoc. Biol. 90: 1159-1166; 2011.