目的 檢測單一免疫球蛋白白細(xì)胞介素1 受體相關(guān)蛋白( SIGIRR) 在正常肺組織及脂多糖( LPS ) 誘導(dǎo)的肺泡上皮細(xì)胞急性損傷中的表達(dá)。方法 收集手術(shù)切除的正常肺組織標(biāo)本20 例,分別采用免疫組織化學(xué)、Western blot、RT-PCR 法檢測SIGIRR 的表達(dá)。以終濃度10 μg/mL的LPS 刺激人Ⅱ型肺泡上皮細(xì)胞來源的A549 細(xì)胞, 于刺激前, 刺激后3、6、12 及24 h 分別以Western blot 法檢測SIGIRR 表達(dá)的變化。將含有SIGIRR cDNA 全長的表達(dá)載體瞬時轉(zhuǎn)染A549 細(xì)胞, 使SIGIRR 在A549 細(xì)胞過表達(dá)。通過MTT 法檢測LPS 對A549 細(xì)胞的損傷作用。結(jié)果 不同檢測方法發(fā)現(xiàn)SIGIRR 在正常肺組織中均有表達(dá); 免疫組織化學(xué)檢測可見SIGIRR 表達(dá)于肺泡上皮細(xì)胞。LPS 刺激后3、6 及12 h 時SIGIRR 表達(dá)較刺激前均下調(diào), 24 h后回升至刺激前水平。MTT 試驗表明過表達(dá)SIGIRR 的A549 細(xì)胞在接受LPS 刺激后生長抑制率顯著低于對照組。結(jié)論 SIGIRR 能夠表達(dá)于正常肺組織, 且能夠減輕LPS 刺激導(dǎo)致的肺泡上皮細(xì)胞損傷。提示SIGIRR 可能參與了LPS 誘導(dǎo)的ALI的調(diào)節(jié)。
引用本文: 田豐,王云杰,趙晉波,張志培,姜濤. SIGIRR 在人正常肺組織及在脂多糖誘導(dǎo)的肺泡上皮細(xì)胞急性損傷中的表達(dá)及意義. 中國呼吸與危重監(jiān)護(hù)雜志, 2009, 09(3): 242-246. doi: 復(fù)制
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2. | Qin J, Qian Y, Yao J, et al. SIGIRR inhibits interleukin-1 receptorand toll-like receptor 4-mediated signaling through different mechanisms. J Biol Chem, 2005, 280: 25233-25241. |
3. | Wald D, Qin J, Zhao Z, et al. SIGIRR, a negative regulator of Tolllike receptor-interleukin 1 receptor signaling. Nat Immunol, 2003 ,4: 920-927. |
4. | Garlanda C, Riva F, Veliz T, et al. Increased susceptibility to colitisassociated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family. Cancer Res, 2007, 67: 6017-6021. |
5. | 修清玉, 錢建美, 王桂芳, 等. 不可分型流感嗜血桿菌誘導(dǎo)A549 細(xì)胞分泌和表達(dá)前炎癥細(xì)胞因子及機(jī)制研究. 中國呼吸與危重監(jiān)護(hù)雜志, 2008, 7: 210-213. |
6. | Garlanda C, Di Liberto D, Vecchi A, et al. Damping excessive inflammation and tissue damage in Mycobacterium tuberculosis infection by Toll IL-1 receptor 8 / single Ig IL-1-related receptor, a negative regulator of IL-1 / TLR signaling. J Immunol, 2007, 179 :3119-3125. |
7. | Adib-Conquy M, Adrie C, Fitting C, et al. Up-regulation of MyD88s and SIGIRR, molecules inhibiting Toll-like receptor signaling, in monocytes from septic patients. Crit Care Med, 2006 , 34: 2377 -2385. |
8. | Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med, 2005, 353: 1685-1693. |
9. | Martin TR, Rubenfeld GD, Ruzinski JT, et al. Relationship between soluble CD14 , lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome. AmJ Respir Crit Care Med, 1997, 155: 937-944. |
10. | Brégeon F, Papazian L, Delpierre S, et al. Role of proinflammatory activity contained in gastric juice from intensive care unit patients to induce lung injury in a rabbit aspiration model. Crit Care Med,2008, 36: 3205-3212. |
11. | Bastarache JA, Wang L, Geiser T, et al. The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor. Thorax, 2007, 62: 608-616. |
12. | Donnarumma G, Paoletti I, Buommino E, et al. Anti-inflammatory effects of moxifloxacin and human beta-defensin 2 association in human lung epithelial cell line ( A549 ) stimulated with lipopolysaccharide. Peptides, 2007, 28: 2286-2292. |
13. | Armstrong L, Medford AR, Uppington KM, et al. Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells. Am J Respir Cell Mol Biol, 2004, 31: 241-245. |
- 1. Thomassen E, Renshaw BR, Sims JE. Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily. Cytokine, 1999, 11: 389-399.
- 2. Qin J, Qian Y, Yao J, et al. SIGIRR inhibits interleukin-1 receptorand toll-like receptor 4-mediated signaling through different mechanisms. J Biol Chem, 2005, 280: 25233-25241.
- 3. Wald D, Qin J, Zhao Z, et al. SIGIRR, a negative regulator of Tolllike receptor-interleukin 1 receptor signaling. Nat Immunol, 2003 ,4: 920-927.
- 4. Garlanda C, Riva F, Veliz T, et al. Increased susceptibility to colitisassociated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family. Cancer Res, 2007, 67: 6017-6021.
- 5. 修清玉, 錢建美, 王桂芳, 等. 不可分型流感嗜血桿菌誘導(dǎo)A549 細(xì)胞分泌和表達(dá)前炎癥細(xì)胞因子及機(jī)制研究. 中國呼吸與危重監(jiān)護(hù)雜志, 2008, 7: 210-213.
- 6. Garlanda C, Di Liberto D, Vecchi A, et al. Damping excessive inflammation and tissue damage in Mycobacterium tuberculosis infection by Toll IL-1 receptor 8 / single Ig IL-1-related receptor, a negative regulator of IL-1 / TLR signaling. J Immunol, 2007, 179 :3119-3125.
- 7. Adib-Conquy M, Adrie C, Fitting C, et al. Up-regulation of MyD88s and SIGIRR, molecules inhibiting Toll-like receptor signaling, in monocytes from septic patients. Crit Care Med, 2006 , 34: 2377 -2385.
- 8. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med, 2005, 353: 1685-1693.
- 9. Martin TR, Rubenfeld GD, Ruzinski JT, et al. Relationship between soluble CD14 , lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome. AmJ Respir Crit Care Med, 1997, 155: 937-944.
- 10. Brégeon F, Papazian L, Delpierre S, et al. Role of proinflammatory activity contained in gastric juice from intensive care unit patients to induce lung injury in a rabbit aspiration model. Crit Care Med,2008, 36: 3205-3212.
- 11. Bastarache JA, Wang L, Geiser T, et al. The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor. Thorax, 2007, 62: 608-616.
- 12. Donnarumma G, Paoletti I, Buommino E, et al. Anti-inflammatory effects of moxifloxacin and human beta-defensin 2 association in human lung epithelial cell line ( A549 ) stimulated with lipopolysaccharide. Peptides, 2007, 28: 2286-2292.
- 13. Armstrong L, Medford AR, Uppington KM, et al. Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells. Am J Respir Cell Mol Biol, 2004, 31: 241-245.