Cutting edge: enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice.
MUC1 (MUC1 in human and Muc1 in nonhumans) is a membrane-tethered mucin that interacts with Pseudomonas aeruginosa (PA) through flagellin. In this study, we compared PA pulmonary clearance and proinflammatory responses by Muc1(-/-) mice with Muc1(+/+) littermates following intranasal instillation of PA or flagellin. Compared with Muc1(+/+) mice, Muc1(-/-) mice showed increased PA clearance, greater airway recruitment of neutrophils, higher levels of TNF-alpha and KC in bronchoalveolar lavage fluid, higher levels of TNF-alpha in media of flagellin-stimulated alveolar macrophages, and higher levels of KC in media of tracheal epithelial cells. Knockdown of MUC1 enhanced flagellin-induced IL-8 production by primary human bronchial epithelial cells. Expression of MUC1 in HEK293T cells attenuated TLR5-dependent IL-8 release in response to flagellin, which was completely ablated when its cytoplasmic tail was deleted. We conclude that MUC1/Muc1 suppresses pulmonary innate immunity and speculate its anti-inflammatory activity may play an important modulatory role during microbial infection.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, 21201, USA.
Wenju
W
Lu
Akinori
A
Hisatsune
Takeshi
T
Koga
Kosuke
K
Kato
Ippei
I
Kuwahara
Erik P
EP
Lillehoj
Wilbur
W
Chen
Alan S
AS
Cross
Sandra J
SJ
Gendler
Andrew T
AT
Gewirtz
K Chul
KC
Kim
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005408:Flagellin / Q000494:pharmacology; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism*; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D051198:Toll-Like Receptor 5 / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D018396:Mucin-1; D034741:RNA, Small Interfering; D051198:Toll-Like Receptor 5; D005408:Flagellin