TNF-α is a key regulator of MUC1, an anti-inflammatory molecule, during airway Pseudomonas aeruginosa infection.
Muc1 is a heterodimeric mucin that is expressed on the apical surface of airway epithelial cells as well as hematopoietic cells. Both in vivo and in vitro studies revealed that Muc1 suppresses inflammatory responses induced by Pseudomonas aeruginosa (PA). In this study, we sought to determine, using intact animals (C57BL/6 mice), whether the expression of Muc1 is important during airway PA infection, and how Muc1 levels are controlled during inflammation. Our results showed that: (1) Muc1 levels in the wild-type (WT) mice were initially low, but gradually increased after PA inhalation, reaching a peak on Day 2, remaining elevated until Day 4, and then gradually decreasing to basal levels on Day 7; (2) TNF receptor 1(-/-) mice failed to increase Muc1 levels after PA infection; (3) after PA inhalation, more inflammatory cells were present in the bronchoalveolar lavage fluid from either Muc1(-/-) or TNF receptor(-/-) mice compared with their WT control animals; (4) more apoptotic neutrophils were present in bronchoalveolar lavage fluid from WT mice compared with Muc1(-/-) mice. We conclude that Muc1(-/-) mice are more inflammatory than WT mice during airway PA infection as a result of both an increase in neutrophil influx and a decrease in neutrophil apoptosis. These results suggest that the up-regulation of Muc1 during airway PA infection might be crucial for suppressing excessive and prolonged inflammatory responses, and is induced mainly by TNF-α, the key proinflammatory mediator.
Choi
Seongwon
S
Immunology and Asthma Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Park
Yong Sung
YS
Koga
Takeshi
T
Treloar
Allison
A
Kim
Kwang Chul
KC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D017209:Apoptosis; D058491:Bacterial Load; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa; D012333:RNA, Messenger / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D018396:Mucin-1; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha
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