TREM-1 inhibition attenuates inflammation and tumor within the colon.

Abstract: The role of myeloid cell receptor TREM-1 as an amplifier of inflammation has been widely accepted and more interestingly, TREM-1 has been implicated in tumorigenesis. However, it is not clear whether TREM-1 links colon inflammation and tumor in vivo. This study aimed to investigate whether inhibition of proinflammatory TREM-1 would prevent aberrant inflammation and tumor development within the colon. In the present study, the mouse model of DSS-induced colitis and colitis-associated tumorigenesis was used. In vivo, the treatment with the TREM-1 antagonist LP17 or control peptide was initiated at the beginning of or after induction of experimental colitis or colitis-associated tumorigenesis. As a result, TREM-1 inhibition by LP17 treatment ameliorated the development of inflammation and tumor within the colon through exerting anti-inflammatory effects. In addition, LP17 decreased intestinal epithelial proliferation in DSS-induced colitis. Taken together, TREM-1 plays critical roles in colon inflammation and tumor and targeting TREM-1 may represent a novel therapeutic strategy for colon inflammation and associated cancer. [Copyright &y& Elsevier]