MUC1 mucin is a negative regulator of toll-like receptor signaling.
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.
Ueno
Keiko
K
Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr., S.E., Albuquerque, NM 87108-5127, USA.
Koga
Takeshi
T
Kato
Kosuke
K
Golenbock
Douglas T
DT
Gendler
Sandra J
SJ
Kai
Hirofumi
H
Kim
K Chul
KC
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000166:cytology; D049410:Luciferases, Renilla / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013223:Statistics as Topic; D051193:Toll-Like Receptors / Q000378:metabolism*; D014132:Trachea / Q000166:cytology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D018396:Mucin-1; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D049410:Luciferases, Renilla