Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095, USA.
Gastroenterology. 2011 Nov;141(5):1852-63.e1-3. doi: 10.1053/j.gastro.2011.06.079. Epub 2011 Jul 14.
BACKGROUND & AIMS: Cathelicidin (encoded by Camp) is an antimicrobial peptide in the innate immune system. We examined whether macrophages express cathelicidin in colons of mice with experimental colitis and patients with inflammatory bowel disease, and we investigated its signaling mechanisms.
Quantitative, real-time, reverse-transcription polymerase chain reaction (PCR), bacterial 16S PCR, immunofluorescence, and small interfering RNA (siRNA) analyses were performed. Colitis was induced in mice using dextran sulfate sodium (DSS); levels of cathelicidin were measured in human primary monocytes.
Expression of cathelicidin increased in the inflamed colonic mucosa of mice with DSS-induced colitis compared with controls. Cathelicidin expression localized to mucosal macrophages in inflamed colon tissues of patients and mice. Exposure of human primary monocytes to Escherichia coli DNA induced expression of Camp messenger RNA, which required signaling by extracellular signal-regulated kinase (ERK); expression was reduced by siRNAs against Toll-like receptor (TLR)9 and MyD88. Intracolonic administration of bacterial DNA to wild-type mice induced expression of cathelicidin in colons of control mice and mice with DSS-induced colitis. Colon expression of cathelicidin was significantly reduced in TLR9(-/-) mice with DSS-induced colitis. Compared with wild-type mice, Camp(-/-) mice developed a more severe form of DSS-induced colitis, particularly after intracolonic administration of E coli DNA. Expression of cathelicidin from bone marrow-derived immune cells regulated DSS induction of colitis in transplantation studies in mice.
Cathelicidin protects against induction of colitis in mice. Increased expression of cathelicidin in monocytes and experimental models of colitis involves activation of TLR9-ERK signaling by bacterial DNA. This pathway might be involved in the pathogenesis of ulcerative colitis.
抗菌肽（由 Camp 编码）是先天免疫系统中的一种抗菌肽。我们研究了实验性结肠炎小鼠和炎症性肠病患者结肠中巨噬细胞是否表达抗菌肽，并研究了其信号转导机制。
进行了定量、实时、逆转录聚合酶链反应（PCR）、细菌 16S PCR、免疫荧光和小干扰 RNA（siRNA）分析。使用葡聚糖硫酸钠（DSS）在小鼠中诱导结肠炎；测量人原代单核细胞中抗菌肽的水平。
与对照组相比，DSS 诱导的结肠炎小鼠炎症性结肠黏膜中抗菌肽的表达增加。抗菌肽表达定位于炎症结肠组织中黏膜巨噬细胞。暴露于人原代单核细胞中的大肠杆菌 DNA 诱导 Camp 信使 RNA 的表达，这需要细胞外信号调节激酶（ERK）信号转导；表达被针对 Toll 样受体（TLR）9 和 MyD88 的 siRNA 减少。将细菌 DNA 腔内给予野生型小鼠可诱导对照小鼠和 DSS 诱导结肠炎小鼠结肠中抗菌肽的表达。TLR9（-/-）小鼠的 DSS 诱导结肠炎中结肠抗菌肽的表达显著降低。与野生型小鼠相比，Camp（-/-）小鼠在 DSS 诱导的结肠炎中表现出更严重的形式，尤其是在给予大肠杆菌 DNA 后。骨髓来源免疫细胞中抗菌肽的表达调节了 DSS 诱导的结肠炎在小鼠移植研究中的发生。
抗菌肽可防止小鼠发生结肠炎。单核细胞和结肠炎实验模型中抗菌肽表达的增加涉及细菌 DNA 激活 TLR9-ERK 信号转导。该途径可能与溃疡性结肠炎的发病机制有关。
