| First Author | Ge Y | Year | 2013 |
| Journal | J Virol | Volume | 87 |
| Issue | 20 | Pages | 11160-7 |
| PubMed ID | 23926349 | Mgi Jnum | J:203873 |
| Mgi Id | MGI:5528950 | Doi | 10.1128/JVI.03099-12 |
| Citation | Ge Y, et al. (2013) Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2. J Virol 87(20):11160-7 |
| abstractText | Nonstructural protein 4 (NSP4), encoded by rotavirus, exhibits various properties linked to viral pathogenesis, including enterotoxic activity. A recent study (O. V. Kavanagh et al., Vaccine 28:3106-3111, 2010) indicated that NSP4 also has adjuvant properties, suggesting a possible role in the innate immune response to rotavirus infection. We report here that NSP4 purified from the medium of rotavirus-infected Caco-2 cells triggers the secretion of proinflammatory cytokines from macrophage-like THP-1 cells and nitric oxide from murine RAW 264.7 cells. Secretion is accompanied by the stimulation of p38 and JNK mitogen-activated protein kinases (MAPKs) and nuclear factor NF-kappaB. NSP4 triggered the secretion of cytokines from murine macrophages derived from wild-type but not MyD88(-/-) or Toll-like receptor 2 (TLR2(-/-)) mice and induced secretion of interleukin-8 (IL-8) from human embryonic kidney cells transfected with TLR2 but not TLR4. Our studies identify NSP4 as a pathogen-associated molecular pattern (PAMP) encoded by rotavirus and provide a mechanism for the production of proinflammatory cytokines associated with the clinical symptoms of infection in humans and animals. |
