Nona-D-arginine amide suppresses corneal cytokines in Pseudomonas aeruginosa keratitis.
Nona-D-arginine amide suppresses corneal cytokines in Pseudomonas aeruginosa keratitis.
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DOI：
10.1097/ico.0b013e3181ca3a69
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发表时间：
2010-11
期刊：
影响因子：
2.8
通讯作者：
Hobden JA
中科院分区：
文献类型：
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作者：
Karicherla P;Aras S;Aiyar A;Hobden JA
九聚-D-精氨酸酰胺（D9R）可在铜绿假单胞菌角膜感染期间抑制白细胞介素-1β（IL-1β）的产生。本研究旨在确定D9R在细胞内的分布情况，以及它对感染诱导的其他炎症介质的影响。
小鼠角膜受伤并接种1×10⁶菌落形成单位（CFU）的铜绿假单胞菌PAO1后，立即每小时向小鼠眼睛滴入5微升磷酸盐缓冲液（PBS，pH 7.4）或100微摩尔的D9R，持续5小时（每只眼睛共滴6次）。在感染后（PI）6小时、12小时和24小时，按照0（眼睛正常）至+4（角膜穿孔）的等级对眼睛进行评分。评分后，处死小鼠并摘除眼球。用整个眼球来测定每只眼睛的活菌CFU数量。切取角膜用于定量检测肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、白细胞介素-10（IL-10）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）。使用标记肽来确定D9R在细胞内的去向。
与用PBS处理的眼睛相比，用D9R处理的眼睛疾病评分显著降低（P≤0.001），活菌CFU数量也更少（P≤0.01）。在任何用D9R处理的眼睛中均未检测到角膜细胞因子。相反，从感染后12小时开始，在PBS处理的眼睛角膜中可检测到数量不断增加的TNF-α、IL-10和GM-CSF。在60分钟内，D9R在细胞核和核仁中积累，并持续存在超过24小时。
D9R部分通过减少细菌载量，部分通过控制具有破坏性的促炎反应，降低了铜绿假单胞菌眼部感染的严重程度。在治疗其他由炎症介导的眼部病变方面，D9R可能是一种可替代类固醇的有效药物 。
Nona-D-arginine amide (D9R) suppressed IL-1β production during Pseudomonas aeruginosa corneal infection. The purpose of this study was to determine the cellular disposition of D9R and its effect on other inflammatory mediators induced by infection. Mouse eyes received 5μl of either phosphate buffered saline (PBS, pH 7.4) or100 μM D9R hourly for 5 hours (total of 6 drops/eye) immediately after corneal wounding and infection with 1× 106 colony forming units (CFU) of P. aeruginosa PAO1. At 6, 12, and 24 hours post infection (PI), eyes were scored on a scale of 0 (normal eye) to +4 (corneal perforation). After scoring, mice were sacrificed and eyes enucleated. Whole eyes were used for determining viable CFU/eye. Corneas were excised for quantitation of TNF-α, IFN-γ, IL-10, and GM-CSF. The fate of D9R in cells was determined using a labeled peptide. Eyes treated with D9R had significantly lower disease scores (P ≤ 0.001) and fewer CFU (P ≤ 0.01) than PBS-treated eyes. No corneal cytokines were detected in any D9R-treated eyes. In contrast, beginning at 12 hours PI, increasing amounts of TNF-α, IL-10, and GM-CSF were detectible in corneas of PBS-treated eyes. Within 60 minutes, D9R accumulated in the cell nucleus and nucleolus and remained for over 24 hours. D9R reduces the severity of P. aeruginosa ocular infection in part by reducing bacterial burden and in part by controlling a destructive pro-inflammatory response. D9R might be a useful alternative to steroids in treating other inflammation-mediated pathologies of the eye.