Five-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside attenuates poly (I:C)-induced airway inflammation in a murine model of asthma.
BACKGROUND
Asthma can frequently be induced or exacerbated by respiratory viral infections. Oxidative stress might also play an essential role in the pathogenesis of allergic airway diseases, indicating that antioxidant therapy may have a potential effect in controlling allergic airway diseases. Recent studies showed that 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) has the potential ability to modulate NADPH oxidase activity, indicating the antioxidant activity of AICAR. This study investigated the inhibitory effects of AICAR as an anti-inflammatory modulator on allergic airway inflammation in murine animal models.


METHODS
The anti-inflammatory effects of AICAR were evaluated in two experimental asthma models: (1) an ovalbumin (OVA)-induced experimental asthma model and (2) an OVA plus polyinosinic-polycytidylic acid [poly (I:C)]-induced experimental asthma model to mimic respiratory viral infections. The inhibitory effects of AICAR in poly (I:C)-mediated signalling for NF-kappaB activation and production of TNF-alpha were analysed in vitro.


RESULTS
AICAR was shown to have a marginal inhibitory effect in an OVA-induced asthma model. Interestingly, AICAR significantly attenuated poly (I:C)-induced airway hyperresponsiveness and airway inflammation, as shown by the attenuation of the influx of total inflammatory cells and soluble products into bronchoalveolar lavage fluid, such as macrophages, eosinophils, IL-5, IL-13, TNF-alpha and IFN-gamma. AICAR also significantly reduced the serum levels of OVA-specific IgE and IgG2a antibodies. Histologic and flow cytometric studies showed that AICAR inhibited poly (I:C)-induced lung inflammation and the infiltration of CD11b+CD11c+ dendritic cells into the lung. Moreover, AICAR effectively inhibited poly (I:C)-mediated activation of NF-kappaB and the production of TNF-alpha.


CONCLUSIONS
These findings suggest that AICAR may be a novel immunomodulator with promising beneficial effects for the treatment of respiratory viral infection in airway allergic diseases.
Kim
T-B
TB
Division of Allergy, University of Ulsan College of Medicine, Seoul, Korea.
Kim
S Y
SY
Moon
K-A
KA
Park
C-S
CS
Jang
M K
MK
Yun
E S
ES
Cho
Y S
YS
Moon
H-B
HB
Lee
K-Y
KY
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011070:Poly I-C / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D012265:Ribonucleotides / Q000494:pharmacology* / Q000627:therapeutic use
D016207:Cytokines; D007136:Immunoglobulins; D007155:Immunologic Factors; D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D010047:Ovalbumin; C031143:AICA ribonucleotide; D011070:Poly I-C