Published ahead of print on December 13, 2007, doi:10.1165/rcmb.2007-0336RC Am. J. Respir. Cell Mol. Biol., Volume 38, Number 3, March 2008, 263-268 A more recent version of this article appeared on March 1, 2008
Submitted on September 15, 2007 MUC1 Mucin Is a Negative Regulator of Toll-like Receptor SignalingKeiko Ueno1,1 Lovelace Respiratory Research Institute, Immunology and Asthma Program, Albuquerque, NM, USA; Department of Molecular Medicine, Global COE "Cell Fate Regulation Research and Education Unit", Kumamoto University, Kumamoto, Japan, 2 Lovelace Respiratory Research Institute, Immunology and Asthma Program, Albuquerque, NM, USA; Department of Chemico-Pharmacology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan, 3 Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA, 4 Department of Biochemistry/Molecular Biology and Tumor Biology Program, Mayo Clinic College of Medicine, Scottsdale, AZ, USA, 5 Department of Molecular Medicine, Global COE "Cell Fate Regulation Research and Education Unit", Kumamoto University, Kumamoto, Japan, 6 Lovelace Respiratory Research Institute, Immunology and Asthma Program, Albuquerque, NM, USA * To whom correspondence should be addressed. E-mail: kckim{at}LRRI.org.
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 using both in vivo and in vitro systems 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.
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