| First Author | Bergeron M | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 9 | Pages | 6271-80 |
| PubMed ID | 17056557 | Mgi Jnum | J:140516 |
| Mgi Id | MGI:3814017 | Doi | 10.4049/jimmunol.177.9.6271 |
| Citation | Bergeron M, et al. (2006) Trypanosoma cruzi-mediated IFN-gamma-inducible nitric oxide output in macrophages is regulated by iNOS mRNA stability. J Immunol 177(9):6271-80 |
| abstractText | Although the effects of activated macrophages (Muphi) on the intracellular parasite Trypanosoma cruzi are well documented, little is known about how host-Muphi functions are affected by this pathogen before activation. This study is aimed at assessing the capacity of T. cruzi infection to modulate J77.4 murine Muphi NO generation following IFN-gamma stimulation, and identifying mechanisms regulating this modulation. Results show that parasite infection potentiates Muphi to produce inducible NO synthase (iNOS) mRNA and protein as well as NO following IFN-gamma stimulation above IFN-gamma alone controls. This potentiation occurs through the concomitant activation of NF-kappaB, ERK1/ERK2 MAPK, and stress-activated protein kinase signaling pathways. Activation of the JAK/STAT pathway by IFN-gamma then leads to STAT1alpha translocation and the transcription of a stable iNOS mRNA species. A decreased rate of iNOS mRNA degradation results in elevated levels of iNOS protein and NO production. Maximal iNOS expression is likely achieved through NF-kappaB activation by T. cruzi, whereas iNOS mRNA stability results from ERK1/ERK2 MAPK and stress-activated protein kinase activation by the infection. Taken together, our data show that T. cruzi-infected Muphi NO generation is controlled at both pre- and posttranscriptional levels and relies on signaling pathway cross-talk. This is the first report of a parasite pathogen capable of heightening host mRNA stability. |
