Background <p>ADAMTSs are extracellular matrix metalloproteinases that mainly process extracellular matrix components and closely related tumorigenesis. ADAMTS-8 is an anti-angiogenic member of the family and is dysregulated in common cancers. The tumor suppressor function of the ADAMTS-8 has been demonstrated in colorectal cancer. Although ADAMTS-8 plays a critical role in tumor progression, transcriptional regulatory features haven’t been studied yet.</p> Materials and methods <p>The human ADAMTS-8 promoter was cloned into the pMetLuc Reporter vector. Basal promoter activity and the effect of the IL-6 on ADAMTS-8 promoter activity were determined by transient transfection assays in SW480 cells. QRT-PCR and Western blot analyses assessed the impact of IL-6 on ADAMTS-8 mRNA and protein expressions. Functional binding of the specific transcription factors to the ADAMTS-8 promoter region was evaluated by ChIP qPCR and EMSA.</p> Results <p>Our results demonstrated that the ADAMTS-8 promoter includes multiple binding sites for transcription factors that could be activated in the inflammatory pathways. IL-6 stimulation increased ADAMTS-8 promoter activity, also mRNA, and protein expressions. Pathway inhibition studies showed that IL-6-mediated induction of ADAMTS-8 was achieved through p38/MAPK, NF-κB, PI3K, and SAPK/JNK pathways. STATs, Elk-1, and c-Jun functionally bind to the ADAMTS-8 promoter region.</p> Conclusion <p>It can be concluded that inflammation is a strong positive regulator of the <i>ADAMTS-8</i> gene.</p>