Immunity, Infection and Inflammation Program, Mater Medical Research Institute, The University of Queensland, Queensland, Australia.
Mucosal Immunol. 2013 May;6(3):557-68. doi: 10.1038/mi.2012.98. Epub 2012 Nov 14.
The MUC1 cell-surface mucin is highly expressed on the gastric mucosal surface, while MUC13 is highly expressed on the intestinal mucosal surface. Polymorphisms in both MUC1 and MUC13 have been linked to inflammatory bowel diseases. MUC1 can act as a decoy molecule on the apical cell surface of epithelial cells and thereby limit bacterial adherence, infection, and inflammation. In this study, we examined whether and how MUC1 and MUC13 modulate infectious and inflammatory signaling. Using gastrointestinal tissue from Muc1- or Muc13-deficient mice in ex vivo culture, MUC1 small interfering RNA (siRNA) silencing in MKN7 gastric epithelial cells, and MUC13 siRNA silencing in LS513 intestinal epithelial cells, we showed that loss of MUC1 increased chemokine secretion, whereas loss of MUC13 decreased chemokine secretion in response to tumor necrosis factor-α. Anti-inflammatory activity of MUC1 and pro-inflammatory activity of MUC13 were also seen after exposure to pathogens, NOD1 (nucleotide-binding oligomerisation domain-containing protein-1), and Toll-like receptor ligands. MUC1 and MUC13 both regulate chemokine secretion in gastrointestinal epithelial cells through a nuclear factor-κB-dependent pathway, although MUC13 modulation could also involve other pathways. Our studies demonstrate that MUC1 and MUC13 are important components of gastrointestinal homeostasis and that disruption or inappropriate expression of these mucins could predispose to infectious and inflammatory disease and inflammation-induced cancer.
黏蛋白 1（MUC1）细胞表面黏蛋白在胃黏膜表面高度表达，而黏蛋白 13（MUC13）在肠黏膜表面高度表达。MUC1 和 MUC13 的多态性与炎症性肠病有关。MUC1 可以作为上皮细胞顶膜表面的诱饵分子，从而限制细菌黏附、感染和炎症。在这项研究中，我们研究了 MUC1 和 MUC13 是否以及如何调节感染和炎症信号。我们使用 Muc1 或 Muc13 缺陷小鼠的胃肠道组织进行离体培养，用 MKN7 胃上皮细胞中的 MUC1 小干扰 RNA（siRNA）沉默，以及 LS513 肠上皮细胞中的 MUC13 siRNA 沉默，结果表明，MUC1 的缺失增加趋化因子的分泌，而 MUC13 的缺失则减少肿瘤坏死因子-α刺激后的趋化因子分泌。在接触病原体、NOD1（核苷酸结合寡聚化结构域包含蛋白-1）和 Toll 样受体配体后，也观察到 MUC1 的抗炎活性和 MUC13 的促炎活性。MUC1 和 MUC13 都通过核因子-κB 依赖途径调节胃肠道上皮细胞中的趋化因子分泌，尽管 MUC13 的调节还可能涉及其他途径。我们的研究表明，MUC1 和 MUC13 是胃肠道稳态的重要组成部分，这些黏蛋白的破坏或表达不当可能导致感染和炎症性疾病以及炎症诱导的癌症。
