Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 19 S1 2020 05 17 74 82 EN Kurosh Kalantar Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran Zahra Farzaneh Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran Nasser Gholijani Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Seyed Younes Hosseini Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran Ebrahim Bani Hasan Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, VIC, Australia AND Department of Medicine-Western Health, The University of Melbourne, St. Albans, VIC, Australia 2019 05 06 2019 09 28 Influenza A virus (IAV) has the potential to cause pandemics with considerable health and socio-economic burdens. A viral protein, polymerase basic 1- frame2 (PB1-F2), as a virulence factor, has pro-apoptotic activity and contributes to viral pathogenesis by delaying viral clearance and inducing inflammation. Macrophages are susceptible to IAV infection and produce high levels of inflammatory cytokines and chemokines. In the present study, the pro-inflammatory effects of PB1-F2 derived peptide was evaluated by measuring the expression of key inflammatory mediators in murine macrophage cell line J774.1. PB1-F2 treated macrophages were examined for nitric oxide (NO) production, inflammatory cytokines, and enzymes expression and pro-inflammatory cytokines secretion using Griess reagent, real-time polymerase chain reaction (PCR) and ELISA, respectively. Our results have shown that PB1-F2 peptide at non-cytotoxic concentrations (0.1–0.8 µmol/mL) had no effect on NO production. When applied to Lipopolysaccharide (LPS)-treated macrophages, PB1-F2 peptide at 0.8 μmol/mLincreasedinducible NO synthase (iNOS), cyclooxygenase (COX)-2, and interleukin (IL)-6 genes expression to 2.02, 3.81, and 3.65 folds, respectively. PB1-F2 at concentrations of 0.4 and 0.8 µm/mL increased tumor necrosis factor (TNF)-α transcription by 4.15 and 5.55 fold. At posttranslational level, TNF-α increased from 166.5±13.88 in LPS-treated cells to 773.6±95.27 and 1485±76.31 at concentrations of 0.4 and 0.8 μmol/mL in PB1-F2 peptide, respectively. However, PB1-F2 Peptide did not have any significant effect on IL-6 production. These findings suggest that PB1-F2 peptide may partly exert its enhancing role in viral pathogenicity through the induction of inflammatory mediators in macrophages. Hence, targeting PB1-F2 peptide would be helpful in the reduction of viral infection complications. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2366