Abstract
Type I interferon (IFN) is induced in virus infected cells, secreted and it inhibits viral replication in neighboring cells. IFN is also an important player in many non-viral diseases and in the development of normal immune cells. Although the signaling pathways for IFN induction by viral RNA or DNA have been extensively studied, its mode of induction in uninfected cells remains obscure. Here, we report that inflammatory cytokines, such as TNF-α and IL-1β, can induce IFN-β through activation of the cytoplasmic RIG-I signaling pathway. However, RIG-I is activated not by RNA, but by PACT, the protein activator of PKR. In cell lines or primary cells expressing RIG-I and PACT, activation of the MAPK, p38, by cytokine signaling, leads to phosphorylation of PACT, which binds to primed RIG-I and activates its signaling pathway. Thus, a new mode of type I IFN induction by ubiquitous inflammatory cytokines has been revealed. KEY POINTS: Cytochalasin D followed by TNF-α / IL-1β treatment activates IFN-β expression.IFN-β expression happens due to activation of RIG-I signaling.Interaction between RIG-I and PACT activates IFN-β expression.