Cutting edge: enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice |
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Authors: | Lu Wenju Hisatsune Akinori Koga Takeshi Kato Kosuke Kuwahara Ippei Lillehoj Erik P Chen Wilbur Cross Alan S Gendler Sandra J Gewirtz Andrew T Kim K Chul |
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Affiliation: | Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, 21201, USA. |
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Abstract: | 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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