Wu Sheng-Hua, Liao Pei-Yuan, Yin Pei-Ling, Zhang Yong-Mei, Dong Ling
Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Am J Pathol. 2009 Jan;174(1):115-22. doi: 10.2353/ajpath.2009.080671. Epub 2008 Dec 18.
Anti-inflammatory effects of the 15-lipoxygenase (15-LO) derivatives lipoxin A(4) (LXA(4)) and 15-S-hydroxyeicosatetraenoic acid (15-S-HETE) have been documented in many experimental models of acute inflammation. However, the expression levels of 15-LO and its products in human renal diseases remain unknown. This study investigated the expression levels of LXA(4), leukotriene B(4) (LTB(4)), and 15-LO in leukocytes and glomeruli obtained from 22 children with acute poststreptococcal glomerulonephritis (APSGN), and determined the modulatory effects of both 15-S-HETE and LXA(4) on LTB(4) synthesis in leukocytes and LTB(4)-evoked chemotaxis of polymorphonuclear leukocytes (PMNs) obtained from children during the first 3 days after onset of APSGN. Expression levels of both LXA(4) and 15-LO in leukocytes and glomeruli were up-regulated during the acute phase of disease, further peaking between days 10 and 14, and remained increased after 6 to 8 weeks of APSGN onset. In contrast, blood and urinary levels of LTB(4) as well as the number of glomerular PMNs peaked during the acute phase of disease and then decreased during the resolution phase. Administration of both 15-S-HETE and LXA(4) in vitro inhibited LTB(4)-induced chemotaxis of PMNs and production of LTB(4) from leukocytes obtained from patients with APSGN. The current study provides further support for an anti-inflammatory role for 15-LO products in human nephritis through both antagonism and inhibition of leukotriene synthesis and its biological activity.
15-脂氧合酶（15-LO）衍生物脂oxin A4（LXA4）和15-S-羟基二十碳四烯酸（15-S-HETE）的抗炎作用已在许多急性炎症实验模型中得到证实。然而，15-LO及其产物在人类肾脏疾病中的表达水平仍不清楚。本研究调查了22例急性链球菌感染后肾小球肾炎（APSGN）患儿白细胞和肾小球中LXA4、白三烯B4（LTB4）和15-LO的表达水平，并确定了15-S-HETE和LXA4对APSGN发病后前3天患儿白细胞中LTB4合成以及LTB4诱导的多形核白细胞（PMN）趋化作用的调节作用。在疾病急性期，白细胞和肾小球中LXA4和15-LO的表达水平均上调，在第10至14天进一步达到峰值，且在APSGN发病6至8周后仍保持升高。相比之下，LTB4的血液和尿液水平以及肾小球PMN数量在疾病急性期达到峰值，然后在缓解期下降。体外给予15-S-HETE和LXA4均抑制了LTB4诱导的APSGN患者PMN趋化作用以及白细胞中LTB4的产生。本研究通过拮抗和抑制白三烯合成及其生物活性，进一步支持了15-LO产物在人类肾炎中的抗炎作用。
