Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 4, Pages 1019-1024Publisher
WILEY
DOI: 10.1002/eji.200838885
Keywords
Gene regulation; IL-32; Inducible nitric oxide synthase; Inflammation; Influenza virus
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Funding
- National Natural Science Foundation of China [30570066]
- Major State Basic Research Development Program of China [2007CB512803, 2009CB522506]
- Hubei Provincial Science Foundation
- Foundation of Ministry of Education of China [20050486012]
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iNOS plays an important role in mediating inflammation. in this study, we found that iNOS-derived NO was increased 2.4-fold in the serum samples of 101 patients infected with influenza A virus in comparison with samples of 105 healthy individuals. in A549 human lung epithelial cells, infection with influenza A virus or stimulation with poly(I:C)+IFN-gamma resulted in increased mRNA and protein levels of both IL-32 and NOS, with subsequent release of NO. Overexpression of IL-32 resulted in upregulated iNOS expression with subsequent No production. Knock down of IL-32 by IL-32-specific siRNA resulted in the inhibition of dsRNA-induced expression of iNOS and NO release, indicating that IL-32 is an upstream regulatory factor of dsRNA-triggered NOS production. Surprisingly, over-expression of iNOS resulted in the reduction of IL-32 expression, and suppression of iNOS by the selective iNOS inhibitor S-methylisothiourea sulfate stimulated IL-32 expression, indicating that a negative feedback mechanism operates between the iNOS/NO and IL-32 systems. These findings suggest that influenza A virus infection activates IL-32 and NOS expression by a heretofore unrecognized complex mechanism, in which the two pro-inflammatory factors regulate each other, involving positive and negative feedback regulatory loops.
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