NF-kappa B/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation.
The NF-kappa B/Rel family of transcription factors induces many genes involved in immune and inflammatory responses. Mice with germline deletions of individual NF-kappa B/Rel subunits have different phenotypes, suggesting that the NF-kappa B/Rel transcription factors have different functions. We tested whether c-Rel promotes allergic asthma using a murine model of allergen-induced pulmonary inflammation and airway hyperresponsiveness. Our investigation focused on c-Rel, which is expressed in lymphoid cells and is important for lymphocyte activation. In response to allergen sensitization and challenge, c-Rel-deficient mice did not develop increases in pulmonary inflammation, bronchoalveolar lavage fluid eosinophilia, or total serum IgE. c-Rel deficiency also prevented the induction of airway hyperresponsiveness. Allergen-treated wild-type mice had increased DNA binding to an NF-kappa B consensus site. Chemokine expression was altered in allergen-treated c-Rel-deficient mice. Monocyte chemoattractant protein-1, which is regulated by NF-kappa B, was decreased in allergen-treated c-Rel-deficient mice relative to wild-type controls. The increase in NF-kappa B/Rel transcription factors after allergen challenge in wild-type mice and the decrease in allergen reactivity found in c-Rel-deficient mice indicate that c-Rel promotes allergic inflammation. Alteration of pulmonary chemokine expression in c-Rel-deficient mice may inhibit allergen-induced pulmonary inflammation and airway hyperresponsiveness.
Donovan
C E
CE
Pulmonary Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
Mark
D A
DA
He
H Z
HZ
Liou
H C
HC
Kobzik
L
L
Wang
Y
Y
De Sanctis
G T
GT
Perkins
D L
DL
Finn
P W
PW
D000336:Aerosols; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007274:Injections, Intraperitoneal; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D020569:Proto-Oncogene Proteins c-rel / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D000336:Aerosols; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D007073:Immunoglobulin E; D010047:Ovalbumin