To elucidate the mechanism that regulates swine host responses, we used specific inhibitors of MAP kinases to pre-treat macrophages before infection. We determined that the induction of IFN-b, IL-6, IL-8, and IL-10 were regulated by ERK1/2, while JNK1/2 may only play a minor or no role in the regulation of these cytokines. As described earlier, IL-1b was not induced in response to the pH1N1 infection, which could be explained by our data indicating that its induction was in fact efficiently suppressed by JNK1/2 in swine macrophages. This may be the first time that JNK1/2 inhibitory effects on the induction of proinflammatory cytokines have been demonstrated. Previous studies found that IFN induction was dependent on the JNK1/2 signaling pathway in epithelial cells infected with influenza virus infection [33] . However, our data clearly demonstrate that ERK1/2 plays a major role in the regulation of IFN-b in pig macrophages, which may indicate that the regulation of IFN differs in different cell types. We noted that basal level activities of both ERK1/2 and JNK1/2 were constitutively present in non-infected 3D/4 cells, which may be important in the induction of proinflammatory and antiviral cytokines at the early stages of infection. Our data indicate that the induction of IL-6, IL-8, IL-10, CCL-5, as well as IFN-b, were apparent at the earliest stages of viral infection even before ERK1/2 was further activated.