Interleukin (IL)-6 is recognized as a factor associated with disease severity in COVID-19. The mechanism underlying the overproduction of IL-6 by SARS-Cov-2 remains unclear. Respiratory viruses initially infect bronchial epithelial cells (BEC) that produce various mediators. We have previously shown that pretreatment of human BEC (NCl-H292) with interferon (IFN)-γ markedly increased poly(I:C)-induced IL-6 production via upregulation of toll-like receptor (TLR) 3. In this study, we further investigated the feature of poly(I:C)-induced IL-6 production in IFN-γ-primed NCl-H292. Priming effects of IFN-γ on poly(I:C)-induced IL-6 production were observed not only in NCl-H292 but also in human primary HBEC and A549, another BEC. The Janus kinase (JAK) inhibitor tofacitinib inhibited IFN-γ-primed upregulation of TLR3 and poly(I:C)-induced IL-6 production. Chromatin immunoprecipitation revealed that IFN-γ stimulated histone modifications at region associated with the IL-6 gene locus. In mouse bronchial inflammation model, IFN-γ priming significantly increased poly(I:C)-induced lung IL-6 mRNA and protein levels in the alveolar lavage fluid. Taken together, priming of bronchial epithelial cells with IFN-γ markedly increases poly(I:C)-induced IL-6 production via JAK-dependent upregulation of TLR3 and chromatin remodeling at IL-6 gene locus. These mechanisms may be involved in severe respiratory inflammation with excess production of IL-6 following infection with RNA viruses.