Trem1 Induces Periodontal Inflammation via Regulating M1 Polarization

Periodontitis is a chronic inflammatory condition characterized by destruction of nonmineralized and mineralized connective tissues. This study evaluated the role of Trem1 (triggering receptors expressed on myeloid cells 1) in periodontitis by influencing polarization of M1 macrophages through the STAT3/HIF-1α signaling pathway. Trem1 was significantly upregulated in the gingival tissues of patients with periodontitis, as identified by high-throughput RNA sequencing, and positively correlated with levels of M1 macrophage-associated genes. The results of flow cytometry, Western blotting, and reverse transcription quantitative polymerase chain reaction showed that knockdown of Trem1 in RAW 264.7 cells decreased polarization of M1 macrophages and increased polarization of M2 macrophages, while overexpression of Trem1 exerted an opposite effect. Furthermore, a mouse model of Trem1 knockout periodontitis exhibited limited infiltration of macrophages and decreased expression levels of M1 macrophage-associated genes in periodontitis lesions and bone marrow-derived macrophages. Importantly, we found that Trem1 could regulate polarization of M1 macrophages through STAT3/HIF-1α signaling as evidenced by RNA sequencing. Moreover, inhibition of Trem1 and HIF-1α could suppress the expression level of proinflammatory cytokine (interleukin 1β) and upregulate the expression level of anti-inflammatory cytokine (interleukin 10) in periodontitis. Collectively, we identified that the Trem1/STAT3/HIF-1α axis could regulate polarization of M1 macrophages and is a potential candidate in the treatment of periodontitis.