Rats susceptible to virus-induced asthma have a persistent virus-induced change in the predominant pulmonary form of the NF-κB inhibitor IκBα.
Weanling Brown Norway (BN) rats are susceptible to persistent steroid-responsive pulmonary abnormalities following resolution of an acute respiratory virus infection. In contrast, Fischer 344 (F344) rats recover without complications. Previous studies determined that NF-κB activation and subunit composition were markedly different between these 2 rat strains. This study examined whether viral infection also resulted in altered pulmonary expression of IκBα and IκBβ, 2 inhibitory regulators of NF-κB. Western blot analyses of total pulmonary protein extracted from BN and F344 rats at 7, 10, and 14 days after inoculation (n = 5 per group) did not reveal virus-induced differences in IκBβ expression. In contrast, a lower molecular weight form of IκBα appeared in the BN rats at 14 days postinfection, and it was still present at 21 days after infection (n = 5 per group). The change in IκBα expression observed in the susceptible BN but not the resistant F344 animals occurs when the epithelium is proliferating during the repair phase, and it correlates with the development of the persistent virus-induced airway inflammation and pulmonary functional abnormalities. These results further implicate differential regulation of NF-κB in the pathogenesis of virus-induced asthma.
Uhl
E W
EW
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388 , USA. euhl@uga.edu
Clarke
T J
TJ
Lester
C
C
Hogan
R J
RJ
D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D020672:I-kappa B Proteins; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D011914:Rats, Inbred BN / Q000378:metabolism / Q000821:virology; D011916:Rats, Inbred F344 / Q000378:metabolism / Q000821:virology; D010253:Respirovirus Infections / Q000150:complications / Q000378:metabolism; D029082:Sendai virus / Q000378:metabolism; D013045:Species Specificity
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D001973:Bromodeoxyuridine