Cutting edge: Enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice

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

Research output: Contribution to journalArticle

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+/+ litter-mates 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-α and KC in bronchoalveolar lavage fluid, higher levels of TNF-α 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 antiinflammatory activity may play an important modulatory role during microbial infection.

Original languageEnglish (US)
Pages (from-to)3890-3894
Number of pages5
JournalJournal of Immunology
Volume176
Issue number7
DOIs
StatePublished - Apr 1 2006

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lu, W., Hisatsune, A., Koga, T., Kato, K., Kuwahara, I., Lillehoj, E. P., Chen, W., Cross, A. S., Gendler, S. J., Gewirtz, A. T., & Kim, K. C. (2006). Cutting edge: Enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice. Journal of Immunology, 176(7), 3890-3894. https://doi.org/10.4049/jimmunol.176.7.3890