Method: In order to test this hypothesis, macrophages from SJL/J and B10.S mice were challenged with TMEV or TLR3 and TLR4 agonists (polyIC and LPS, respectively) and IL-6 expression was evaluated by qRT-PCR and ELISA. To determine the role of ERK and p38 MAP-kinase signaling pathways in IL-6 expression and TMEV replication, macrophages were pretreated with the p38 MAPK inhibitor, SB203580, or the ERK-MAPK inhibitor, U0126, before challenged with TMEV. To determine if pretreatment with IFNb or IL-12 could influence TMEV induced IL-6 expression, SJL/J and B10.S macrophages were pretreated with recombinant IFNb, IL-12p70, or IL-12p40.
Result: The results show that macrophages stimulated with TMEV, polyIC, or LPS express IL-6 but SJL/J macrophages produce significantly more IL-6 mRNA and significantly less IL-6 protein than B10.S macrophages. In contrast to SB203580, U0126 significantly lowered TMEV-induced IL-6 expression but significantly increased TMEV replication in macrophages. IL-12 dramatically, and to a lesser extent IFNb, augmented IL-6 expression from TMEV-infected macrophages of both mouse strains.
Conclusion: Therefore, murine macrophages express high levels of IL-6 in response to TMEV in a TLR/ERK-MAP-kinase dependent manner. However, SJL/J macrophages produce less IL-6 in response to TMEV infection than B10.S, which may be related to decreased IL-12 from TMEV-infected SJL/J macrophages compared with B10.S macrophages. The data suggest that IL-6 and ERK-MAP-kinases have an unknown role in innate anti-viral immunity.
Keywords: Cell biology, Cytokine and Immunology
See more of: Microbiology / Immunology