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MUC1 Mucin Is a Negative Regulator of Toll-Like Receptor Signaling

¹ Immunology and Asthma Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico; Departments of ² Molecular Medicine, Global COE "Cell Fate Regulation Research and Education Unit," and ³ Chemico-Pharmacology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Japan; ⁴ Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts; and ⁵ Department of Biochemistry/Molecular Biology & Tumor Biology Program, Mayo Clinic College of Medicine, Scottsdale, Arizona

Correspondence and requests for reprints should be addressed to K. Chul Kim, Ph.D., Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr., S.E., Albuquerque, NM 87108-5127. 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 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.

Key Words: MUC1/Muc1 • Toll-like receptors • anti-inflammatory • NF-B • TNF-

CLINICAL RELEVANCE This new finding that MUC1 can suppress the activity of all the Toll-like receptors has great potential for clinical applications in controlling excessive and prolonged airway inflammation during airway infection.