A20 attenuates allergic airway inflammation in mice.
TNF receptor 1 can activate signaling pathways leading to the activation of NF-kappaB. A20, an NF-kappaB-inducible protein, negatively regulates these signaling pathways and acts as an anti-inflammatory mediator. Therefore, A20 is viewed as a potential therapeutic target for inflammatory disease. In this study, we examined the effect of A20 on an OVA-induced allergic airway inflammation model in mice. We used an adenovirus containing A20 cDNA (Ad-A20) that was delivered intratracheally before OVA challenge. Single administration of Ad-A20 reduced airway inflammatory cell recruitment and peribronchiolar inflammation and suppressed the production of various cytokines in bronchoalveolar fluid. In addition, Ad-A20 suppressed mucus production and prevented the development of airway hyperresponsiveness. The protective effect of Ad-A20 was mediated by the inhibition of the NF-kappaB signaling pathway. Taken together, our results suggest that the development of an immunoregulatory strategy based on A20 may have therapeutic potential for the treatment of allergic asthma.
Kang
Nam-In
NI
Department of Immunology, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk, Republic of Korea.
Yoon
Ha-Yong
HY
Lee
Young-Rae
YR
Won
Minho
M
Chung
Myoung Ja
MJ
Park
Jin-Woo
JW
Hur
Gang Min
GM
Lee
Hern-Ku
HK
Park
Byung-Hyun
BH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D005822:Genetic Vectors / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy*; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D010047:Ovalbumin; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse