MUC1 mucin is a negative regulator of toll-like receptor signaling

Am J Respir Cell Mol Biol. 2008 Mar;38(3):263-8. doi: 10.1165/rcmb.2007-0336RC. Epub 2007 Dec 13.

Abstract

MUC1 (MUC1 in humans and Muc1 in nonhuman species) is a transmembrane mucin-like glycoprotein expressed in epithelial cells lining various mucosal surfaces as well as hematopoietic cells. Recently, we showed that Muc1(-/-) mice exhibited greater inflammatory responses to Pseudomonas aeruginosa or its flagellin compared with their wild-type littermates, and our studies with cultured cells revealed that MUC1/Muc1 suppressed the Toll-like receptor (TLR) 5 signaling pathway, suggesting its anti-inflammatory role. Here we demonstrate that other TLR signaling (TLR2, 3, 4, 7, and 9) is also suppressed by MUC1/Muc1. The results from this study suggest that MUC1/Muc1 may play a crucial role during airway infection and inflammation by various pathogenic bacteria and viruses.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Chemokine CXCL1 / analysis
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL1 / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / metabolism
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Kidney / cytology
  • Luciferases, Renilla / metabolism
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Knockout
  • Mucin-1 / genetics*
  • Mucin-1 / metabolism*
  • Recombinant Proteins / metabolism
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism
  • Signal Transduction*
  • Statistics as Topic
  • Toll-Like Receptors / metabolism*
  • Trachea / cytology
  • Transfection
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Mucin-1
  • Recombinant Proteins
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Luciferases, Renilla