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item Loving, Crystal
item Brockmeier, Susan
item Sacco, Randy

Submitted to: American Association of Immunologists Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 4/13/2006
Publication Date: 5/15/2006
Citation: Loving, C.L., Brockmeier, S., Sacco, R.E. 2006. Differential regulation of type I interferon activation in macrophages [abstract]. American Association of Immunologists Proceedings. 249:43-44.

Interpretive Summary:

Technical Abstract: Pulmonary airways are relatively vulnerable to infection because of continuous exposure to antigen during respiration. The innate immune response must be activated promptly, yet incisively, after pathogen recognition. Alveolar macrophages (AM) play a role in initiating the antiviral response in the lung. TLR3 and PKR recognize double-stranded RNA (dsRNA), an intermediate of viral replication, and initiate the transcription of type I interferons (IFN-alfa/beta). Synthetic dsRNA (polyIC) was used to investigate the innate response in porcine AM’s and compared to that of peritoneal macrophages (PM). PolyIC triggered transcription of IFN-alfa/beta in AM’s and PM’s, but mRNA levels in AM’s were significantly higher. However, the transcription of downstream genes, Mx and PKR, was significantly less in AM’s than PM’s. The lack of Mx and PKR transcription in AM’s was not due to a defective IFN-alfa/beta receptor (IFNAR), as stimulation with recombinant IFN-alfa induced phosphorylation and translocation of STAT-1 into the nucleus. To investigate the differential regulation of IFN-alfa/beta activation, 2-aminopurine (2-AP) was used to block the activation of PKR by dsRNA. IFN-alfa/beta mRNA levels in AM’s after polyIC treatment were unaffected by 2-AP, whereas PM’s treated with 2-AP plus polyIC showed a significant decrease in IFN-alfa/beta transcription. There was a significant increase in Mx and PKR mRNA levels in 2-AP plus polyIC treated AM’s, but a significant decrease in PM’s. PKR is likely involved in the induction of IFN-alfa/beta transcription in PM’s, but not AM’s. In addition, there appears to be a block in (IFN-alfa/beta) mRNA translation in AM’s that is removed by inhibiting PKR activation.