Cutting Edge: Enhanced Pulmonary Clearance of Pseudomonas aeruginosa by Muc1 Knockout Mice | Zendy

Wenju Lu | Zendy; Akinori Hisatsune | Zendy; Takeshi Koga | Zendy; Kosuke Kato | Zendy; Ippei Kuwahara | Zendy; Erik P. Lillehoj | Zendy; Wilbur Chen | Zendy; Alan S. Cross | Zendy; Sandra Gendler | Zendy; Andrew T. Gewirtz | Zendy; K. Chul Kim | Zendy

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Cutting Edge: Enhanced Pulmonary Clearance of Pseudomonas aeruginosa by Muc1 Knockout Mice

Author(s) -

Wenju Lu,

Akinori Hisatsune,

Takeshi Koga,

Kosuke Kato,

Ippei Kuwahara,

Erik P. Lillehoj,

Wilbur Chen,

Alan S. Cross,

Sandra Gendler,

Andrew T. Gewirtz,

K. Chul Kim

Publication year - 2006

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.176.7.3890

Subject(s) - flagellin , tlr5 , proinflammatory cytokine , muc1 , mucin , gene knockdown , chemistry , pseudomonas aeruginosa , bronchoalveolar lavage , tumor necrosis factor alpha , microbiology and biotechnology , inflammation , immunology , biology , innate immune system , medicine , lung , toll like receptor , immune system , biochemistry , bacteria , receptor , genetics , apoptosis

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.

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