mtDAMPS inhibit lung epithelial cell via activating TREM-1 and cGAS-STING pathway in macrophage

Background: The release of mitochondrial damage-associated molecular patterns (mtDAMPs) from kidneys with acute kidney injury (AKI) is a significant contributor for distant organ damage. Methods: The mice lung bronchus cell line MM14.LU and lung macrophage cell line AMJ2-C8 were utilized to study the mechanisms of how mtDAMPs induce lung damage. mtDAMPs were isolated from mice kidney, and cells were treated with different concentration of mtDAMPs. Westen blot, qPCR and ELISA were used to determine the protein and RNA expression level of TREM-1, cGAS and STING. Results: The bronchus cells did not respond to mtDAMPs, the mRNA expressions of TREM-1, cGAS and STING exhibited no significant differences compared to the control group; however, when co-culture bronchus cells along with macrophage, WB, qPCR and ELISA results showed that TREM-1 and cGAS-STING pathway were upregulated in the mtDAMPs treated cells. Electric Cell-substrate Impedance Sensing (ECIS) results demonstrated that mtDAMPs treated cells have decreased proliferation, and inhibiting the TREM-1 and cGAS-STING pathway significantly increased cell proliferation. Conclusion: Our findings indicated that targeting TREM-1 and cGAS-STING has the potential to reduce acute lung injury caused by mtDAMPs in vitro. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.