In rheumatoid arthritis (RA), tumor necrosis factor alpha (TNFα) and interleukin 17 (IL-17A) are elevated in the synovial fluid. They synergistically activate production of cytokines such as IL-6, a key target of biologic therapies. Since synovial fibroblasts are the major source of IL-6 in the joint, we wanted to understand regulation of IL-6 production. With synovial fibroblasts from 7 patients with osteoarthritis or RA, we used RNA-seq to measure response to TNFα and different dosages of IL-17 (0, 1, and 10 ng/mL) at 8 time points over 24 hours. 409 genes (FDR < 0.01) had expression proportional to IL-17 dose, including genes regulated by Nuclear factor kappa B (NFκB). However, NFκB expression was not proportional to IL-17 dose. We discovered two regulatory mechanisms: one mediated by NFκB inhibitor zeta (NFKBIZ) and the other by Cut Like Homeobox 1 (CUX1). NFKBIZ expression was proportional to IL-17 dose. Silencing NFKBIZ with siRNA caused 82% reduction in protein levels of IL-6, IL-8 (CXCL8), and MMP3 after costimulation by TNFα and IL-17, but only 8% reduction after stimulation with TNFα alone, suggesting NFKBIZ mediates inflammation only after costimulation. In contrast, CUX1 expression was not proportional to IL-17 dose. After costimulation, we found that CUX1 binds NFκB and is recruited to a CUX1-NFκB motif unique to the promoters of CXCL1, CXCL2, and CXCL3. Silencing CUX1 significantly reduced neutrophil recruitment in vitro. In summary, we characterized the transcriptional response to TNFα and IL-17 and identified NFKBIZ and CUX1 as key regulators of fibroblast mediated inflammation.