Luteolin up-regulates the production of type I and II interferons in MARC-145 cells in response to porcine reproductive and respiratory syndrome virus infection

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is an immunosuppressive infectious disease in pigs. Due to the absence of effective therapeutic drugs against PRRSV and the limitations of existing commercial PRRS vaccines, adequate protection cannot be provided to pigs. PRRS has resulted in considerable economic losses in the global pig industry. Therefore, there is an urgent need for new and efficient prevention strategies for this disease. Luteolin, a natural flavonoid in various plants, demonstrates multiple biological activities, including antioxidant, anti-inflammatory, and antiviral effects. However, little is known about the antiviral activity of luteolin against PRRSV and its impact on the production of antiviral cytokines following PRRSV infection. Here, we evaluated the activity of luteolin against PRRSV and determined that the safe concentration of luteolin for MARC-145 cells was not more than 50 μM. Luteolin showed dose- and time-dependent inhibition of PRRSV replication in MARC-145 cells. PRRSV infection was found not to affect the expression of interferon-α (IFN-α), IFN-β, IFN-γ, and tumor necrosis factor-α (TNF-α) transcripts and proteins in MARC-145 cells. Still, it up-regulated the expression of interleukin-10 (IL-10) transcript and protein in MARC-145 cells. By contrast, luteolin treatment up-regulated the expression of IFN-α, IFN-β, IFN-γ, and IL-10 transcripts and proteins and down-regulated the expression of TNF-α transcript and protein in MARC-145 cells. In addition, luteolin treatment of MARC-145 cells infected by PRRSV up-regulated the expression of IFN-α, IFN-β, IFN-γ, and IL-10 and down-regulated the expression of TNF-α at both the transcript and protein levels. In summary, this study indicated that luteolin might inhibit the proliferation of PRRSV in MARC-145 cells by inducing an innate antiviral response via up-regulating the synthesis of type I and II IFNs, which highlighted the potential of luteolin as an anti-PRRSV drug and provided a reference for the development of future treatments against PRRSV infection.