Secretory leukocyte protease inhibitor inhibits expression of polymeric immunoglobulin receptor via the NF-κB signaling pathway
Secretory leukocyte protease inhibitor inhibits expression of polymeric immunoglobulin receptor via the NF-κB signaling pathway
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DOI：
10.1016/j.molimm.2015.07.021
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发表时间：
2015-10-01
影响因子：
3.6
通讯作者：
Komiyama, Kazuo
中科院分区：
文献类型：
--
作者：
Mikami, Yoshikazu;Iwase, Takashi;Komiyama, Kazuo
聚合免疫球蛋白受体（pIgR）在粘膜免疫系统中起着重要的作用。分泌性免疫球蛋白A由pIgR的分泌组分和二聚体形式的免疫球蛋白A组成，分泌于粘膜表面，是一种生物防御因子。据报道，pIgR基因的表达是由转录因子核因子(NF)-kappa b的激活诱导的。另一方面，分泌性白细胞蛋白酶抑制剂（SLPI）是一种糖蛋白，具有丝氨酸蛋白酶抑制剂的功能。在肺泡上皮细胞中，SLPI增加了I κ B β的水平，这表明它在蛋白水平上是nf - κ B的抑制剂。综上所述，SLPI可能调控plgR的表达；然而，这种情况发生的具体机制尚不清楚。因此，本研究的目的是阐明SLPI对pIgR表达的影响。SLPI和pIgR分别定位于胃肠道杯状细胞和纤毛上皮细胞。未检测到SLPI和pIgR共表达的细胞。此外，重组人SLPI刺激上皮细胞系（HT-29）可降低pIgR的表达。在slpi缺失的Ca9-22细胞中pIgR的表达也高于野生型Ca9-22细胞。此外，利用NF-kappa B报告质粒进行荧光素酶测定和实时RT-PCR分析表明，当SLPI存在时，NF-kappa B蛋白的转录活性被抑制，同时伴随着I -kappa B β蛋白的表达增加，但mRNA的表达不增加。这些结果表明，SLPI通过抑制I κ B β蛋白的降解，通过nf - κ B信号通路下调pIgR的表达。(C) 2015年作者。Elsevier Ltd.出版。
Polymeric immunoglobulin receptor (pIgR) plays an important role in mucosal immune systems. Secretory immunoglobulin A, composed of secretory component of pIgR and a dimeric form of immunoglobulin A, is secreted on mucosal surfaces and serves as a biological defense factor. pIgR gene expression is reportedly induced by activation of the transcription factor nuclear factor (NF)-kappa B. On the other hand, secretory leukocyte protease inhibitor (SLPI) is a glycoprotein that functions as a serine protease inhibitor. In alveolar epithelial cells, SLPI increases the level of I kappa B beta, which indicates that it is an inhibitor of NF-kappa B at the protein level. Taken together, SLPI may regulate plgR expression; however, the specific mechanism by which this occurs is unclear. Therefore, the aim of this study was to elucidatethe influence of SLPI on pIgR expression. SLPI and pIgR localized in goblet cells and ciliated epithelial cells of the gastrointestinal tract, respectively. No cells were detected in which SLPI and pIgR were co-expressed. In addition, recombinant human SLPI stimulation of an epithelial cell line (HT-29) decreased the pIgR expression. The pIgR expression was also higher in SLPI-deficient Ca9-22 cells than in wild-type Ca9-22 cells. Furthermore, a luciferase assay using a NF-kappa B reporter plasmid and real-time RT-PCR analysis indicated that when SLPI was present, the transcriptional activity of NF-kappa B protein was suppressed, which was accompanied by anincrease in the protein, but not the mRNA,expression of I kappa B beta. These results demonstrate that SLPI down-regulates pIgR expression through the NF-kappa B signaling pathway by inhibiting degradation of I kappa B beta protein. (C) 2015 The Authors. Published by Elsevier Ltd.