MicroRNA-155 is induced during the macrophage inflammatory response. This study identifies miR-155 as a miRNA significantly up-regulated by both poly(I:C) and IFN-β in primary murine macrophages. It is also induced by several Toll-like receptor (TLR) ligands through MyD88- or TRIF-dependent pathways, while IFN-induced up-regulation involves TNF-α autocrine signaling. Pharmacological inhibition of the kinase JNK blocked miR-155 induction by both poly(I:C) and TNF-α, suggesting the JNK pathway is involved in miR-155 regulation. These findings show that miR-155 is a common target of various inflammatory mediators. Since miR-155 is known to function as an oncogene, these results suggest a potential link between inflammation and cancer. The mammalian innate immune response is crucial for pathogen detection through pattern recognition receptors like TLRs. TLRs signal through MyD88 or TRIF adaptors to activate pathways such as NF-κB, MAPKs, and IRF family members, which coordinate gene expression to initiate microbial clearance. However, these pathways can also contribute to cancer and autoimmunity under pathological conditions. miRNAs, non-coding RNA molecules, are highly conserved and regulate gene expression. They are involved in various biological processes, including development and cancer. miRNA expression is regulated by inflammatory stimuli, and recent studies show that miRNAs can be altered by bacterial endotoxins and may regulate innate immune responses. The study shows that miR-155 is induced by various inflammatory mediators, including TLR ligands and IFNs. miR-155 is encoded by the BIC gene and is involved in the inflammatory response. The regulation of miR-155 involves BIC mRNA up-regulation by poly(I:C) or IFN-β. miR-155 is an immediate early target gene of poly(I:C)-induced signaling, while its induction by IFN-β is delayed. TLRs induce miR-155 through MyD88- or TRIF-dependent signaling pathways. IFN-β and IFN-γ induce miR-155 through TNF-α autocrine/paracrine signaling. The JNK pathway is involved in miR-155 induction by TLRs and TNF-α. These findings suggest that miR-155 is a component of the primary macrophage response to inflammatory mediators and may link inflammation and cancer. The study highlights the role of miR-155 in innate immunity and cancer biology.MicroRNA-155 is induced during the macrophage inflammatory response. This study identifies miR-155 as a miRNA significantly up-regulated by both poly(I:C) and IFN-β in primary murine macrophages. It is also induced by several Toll-like receptor (TLR) ligands through MyD88- or TRIF-dependent pathways, while IFN-induced up-regulation involves TNF-α autocrine signaling. Pharmacological inhibition of the kinase JNK blocked miR-155 induction by both poly(I:C) and TNF-α, suggesting the JNK pathway is involved in miR-155 regulation. These findings show that miR-155 is a common target of various inflammatory mediators. Since miR-155 is known to function as an oncogene, these results suggest a potential link between inflammation and cancer. The mammalian innate immune response is crucial for pathogen detection through pattern recognition receptors like TLRs. TLRs signal through MyD88 or TRIF adaptors to activate pathways such as NF-κB, MAPKs, and IRF family members, which coordinate gene expression to initiate microbial clearance. However, these pathways can also contribute to cancer and autoimmunity under pathological conditions. miRNAs, non-coding RNA molecules, are highly conserved and regulate gene expression. They are involved in various biological processes, including development and cancer. miRNA expression is regulated by inflammatory stimuli, and recent studies show that miRNAs can be altered by bacterial endotoxins and may regulate innate immune responses. The study shows that miR-155 is induced by various inflammatory mediators, including TLR ligands and IFNs. miR-155 is encoded by the BIC gene and is involved in the inflammatory response. The regulation of miR-155 involves BIC mRNA up-regulation by poly(I:C) or IFN-β. miR-155 is an immediate early target gene of poly(I:C)-induced signaling, while its induction by IFN-β is delayed. TLRs induce miR-155 through MyD88- or TRIF-dependent signaling pathways. IFN-β and IFN-γ induce miR-155 through TNF-α autocrine/paracrine signaling. The JNK pathway is involved in miR-155 induction by TLRs and TNF-α. These findings suggest that miR-155 is a component of the primary macrophage response to inflammatory mediators and may link inflammation and cancer. The study highlights the role of miR-155 in innate immunity and cancer biology.