Abstract:
:Nrf2 is a leucine zipper transcription factor that protects against oxidant-induced injury. Nontypeable Haemophilus influenzae is responsible for frequent disease exacerbations in patients with chronic obstructive pulmonary disease and is responsible for causing otitis media in young children. We hypothesized that Nrf2 would limit inflammatory responses to nontypeable H. influenzae. The objective of this study was to assess the role of Nrf2 in chronic lung inflammation and regulation of immune responses to nontypeable H. influenzae in mice. Wild-type (C57BL/6) mice and Nrf2(-/-) mice were instilled by oropharyngeal aspiration of 1 × 10(6) colony-forming units of live, nontypeable H. influenzae (NTHI) twice a week for 4 to 16 consecutive weeks to generate a chronic inflammatory milieu within the lungs that models chronic bronchitis. Nrf2(-/-) mice had increased lymphocytic airway inflammation compared with WT mice after NTHI challenge. Although the extent of NTHI-induced peribronchovascular inflammation did not significantly differ between the genotypes, plasma cell infiltration was significantly more abundant in Nrf2(-/-) mice. Most strikingly, Nrf2(-/-) mice generated significantly enhanced and persistent levels of serum antibodies against P6, a key outer membrane protein of NTHI. Lung dendritic cells from Nrf2(-/-) mice challenged with NTHI had increased activation markers compared with dendritic cells from similarly treated WT mice. Nrf2 regulates NTHI-induced airway inflammation characterized by lymphocytic and plasma cell infiltration and the activation of lung dendritic cells and B-cell responses in mice. Nrf2 may be a potential therapeutic target in limiting the bacterial infection-induced airway inflammation that drives exacerbations of chronic obstructive pulmonary disease.
journal_name
Am J Respir Cell Mol Biolauthors
Lugade AA,Vethanayagam RR,Nasirikenari M,Bogner PN,Segal BH,Thanavala Ydoi
10.1165/rcmb.2010-0321OCsubject
Has Abstractpub_date
2011-09-01 00:00:00pages
557-65issue
3eissn
1044-1549issn
1535-4989pii
2010-0321OCjournal_volume
45pub_type
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