Activation of toll-like receptor 4/nuclear factor-kappa B signaling by triggering a receptor expressed on myeloid cells 1 promotes alveolar macrophage M1 polarization and exacerbates septic acute lung injury

Background: Septic acute lung injury (ALI) is a life-threatening condition commonly occurring in the intensive care unit. Inflammation is considered as the basic pathological response of septic ALI. Triggering receptor expressed on myeloid cells 1 (TREM1) is a member of the immunoglobulin superfamily receptors that regulates the inflammatory response. However, the role of TREM1 in septic ALI has not yet been reported.

Methods: Cell viability was tested using the MTT assay. TdT-mediated dUTP nick end labeling assay and flow cytometry were used for apoptosis. The level of protein was detected using western blot analysis. The levels of tumor necrosis factor-α and interleukin-1β were assessed using enzyme-linked immunosorbent assay. The lactate dehydrogenase content was assessed using the assay kit. Myeloperoxidase activity was determined using an assay. Histology of lung tissue was further analyzed through hematoxylin-eosin staining.

Results: We found that TREM1 knockdown by transfection with si-TREM1 inhibited lipopolysaccharide (LPS)-induced cell apoptosis of alveolar macrophage cell line MH-S. The LPS stimulation caused M1 polarization of MH-S cells, which could be reversed by TREM1 knockdown. In vivo assays proved that si-TREM1 injection improved lung injury and inflammation of cecal ligation and puncture-induced ALI in mice. In addition, TREM1 knockdown suppressed the activation of toll-like receptor 4/nuclear factor-kappa B signaling, implying the involvement of TLR4 in the effects of TREM1 in response to LPS stimulation.

Conclusions: This study examined the proinflammatory role of TREM1 in septic ALI and its regulatory effect on alveolar macrophage polarization. These results suggest that TREM1 could potentially serve as a therapeutic target in the prevention and treatment of ALI.