Triggering receptor expressed on myeloid cells (TREM)-1 is expressed in macrophages, and functions as an amplifying molecule in inflammatory responses. TREM-1 is constitutively expressed in macrophage, and upregulated by bacterial components, such as lipopolysaccharide (LPS). In this present study, we investigated the regulatory mechanism for the basal and LPS-induced transcription of mouse TREM-1 gene in mononuclear cells using RAW264.7 macrophage-like cells.To elucidate the potential role of cis-acting elements in the basal and LPS-induced transcription of mouse TREM-1 gene, the luciferase vector containing the promoter with 5' deletion and adenine substitution mutants was transfected into RAW264.7 cells and incubated in the absence or presence of LPS. To further identify the transcription factor(s), gel shift/supershift analysis was performed.The CRE (cAMP response element) and NF-κB-1 (a distal NF-κB site) in the mouse TREM-1 promoter are positively and negatively regulating the basal TREM-1 transcription via the interaction with C/EBPα and NF-κB p50/p50 homodimer, respectively. In addition, the CRE and NF-κB-1 likely participate in the LPS-induced upregulation of TREM-1 promoter activity possibly via the interaction with phosphorylated CREB and NF-κB p65/p50 heterodimer. Furthermore, the AP-1-1 (a distal AP-1 site) is likely to be involved in the LPS-induced TREM-1 transcription via the interaction with phosphorylated c-fos/c-jun.The present study has demonstrated for the first time the detailed mechanism for the basal and LPS-induced expression of TREM-1, an amplifying molecule in inflammation.