Upon ORM2 stimulation, NF-κB and p38 MAP kinase are major downstream pathways for the robust production of proinflammatory cytokines and chemokines, including IL-6, TNF-α, CXCL8, and CCL2, by macrophages and RA-FLSs. The gene discussed is NFKB1; the disease is rheumatoid arthritis.