Interleukin-8/CXCL8 forms an autocrine loop in fetal intestinal mucosa
Interleukin-8/CXCL8 forms an autocrine loop in fetal intestinal mucosa
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DOI：
10.1203/01.pdr.0000133196.25949.98
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发表时间：
2004-08-01
影响因子：
3.6
通讯作者：
Calhoun, DA
中科院分区：
文献类型：
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作者：
Maheshwari, A;Lacson, A;Calhoun, DA
IL-8/CXC配体（CXCL）8以高浓度被人胎儿/新生儿与羊水和人乳一起摄取，并且也由肠上皮细胞（IEC）组成性地产生。我们已经证明，重组人IL-8/CXCL 8（rhIL-8/CXCL 8）保护培养的IEC免受肿瘤坏死因子（TNF）-α和环己酰亚胺诱导的细胞毒性。鉴于其组成性生产，我们假设IL-8/CXCL 8可能在胎儿肠上皮细胞的维护中发挥自分泌作用。在这项研究中，我们测量了IL-8/CXCL 8 mRNA在胎儿肠道（妊娠11-22周）的浓度，寻找存在的蛋白质在胎儿胃和肠（9-24周），测量新生儿胃分泌物中的IL-8/CXCL 8，并研究了组成和刺激的IL-8/CXCL 8在培养IEC的表达。我们发现IL-8/CXCL 8在胎儿肠组织中的转录和表达是一致的，与妊娠成熟呈发育调节的负相关。IL-8/CXCL 8的同源受体也在胎儿肠中大量表达，因此，我们试图确定表达的IL-8/CXCL 8是否会完成自分泌环。IL-8/CXCL 8的中和导致在TNF-α存在下培养的IEC中细胞死亡增加。这种作用是通过CXCR 2受体特异性介导的。我们推测，IL-8/CXCL 8分泌细胞毒应激反应的细胞自我防御机制。
IL-8/CXC ligand (CXCL) 8 is ingested in high concentrations by the human fetus/neonate with amniotic fluid and human milk, and is also produced constitutively by intestinal epithelial cells (IEC). We have shown that recombinant human IL-8/CXCL8 (rhIL-8/CXCL8) protects cultured IEC against tumor necrosis factor (TNF)-alpha and cycloheximide-induced cytotoxicity. In view of its constitutive production, we hypothesized that IL-8/CXCL8 might play an autocrine role in fetal enterocyte maintenance. In this study, we measured IL-8/CXCL8 mRNA concentrations in fetal intestine (11-22 wk gestation), sought the presence of the protein by immunohistochemistry in fetal stomach and intestine (9-24 wk), measured IL-8/CXCL8 in neonatal gastric secretions, and studied constitutive and stimulated IL-8/CXCL8 expression in cultured IEC. We found that IL-8/CXCL8 is consistently transcribed and expressed in fetal intestinal tissue, in a developmentally regulated inverse relationship with gestational maturation. The cognate receptors for IL-8/CXCL8 are also expressed abundantly in the fetal intestine, and, therefore, we sought to determine whether the expressed IL-8/CXCL8 would complete an autocrine loop. Neutralization of IL-8/CXCL8 resulted in increased cell death in cultured IEC in the presence of TNF-alpha. This effect is specifically mediated through the CXCR2 receptors. We speculate that IL-8/CXCL8 secretion during cytotoxic stress reflects a cellular self-defense mechanism.