GNG7 attenuates inflammation and modulates macrophage function via the NF-κB/NLRP3 inflammasome pathways in Poly I:C-induced acute lung injury.

Acute lung injury (ALI) is driven by excessive inflammation, but the molecular regulation of macrophage responses remain incompletely defined. This study investigated the role of G protein gamma subunit 7 (GNG7) in mediating inflammatory signaling in cell and mouse models of ALI. RAW264.7 macrophages were stimulated with Poly I:C and subjected to GNG7 knockdown or overexpression. Inflammatory cytokines, reactive oxygen species (ROS), phagocytic activity, and NF-κB/NLRP3 inflammasome signaling were evaluated using qRT-PCR, ELISA, fluorescence imaging and Western blotting. RNA sequencing followed by GO and KEGG analyses was performed after GNG7 knockdown. NF-κB/NLRP3 pathway involvement was examined using inhibitors BAY 11-7082 and MCC950. In vivo, Poly I:C-induced ALI mice received AAV9-sh-GNG7, followed by assessment of lung pathology, bronchoalveolar lavage fluid cytokines, and macrophage polarization markers. Poly I:C stimulation markedly upregulated GNG7 expression, whereas GNG7 knockdown caused broad transcriptomic changes enriched in virus-responsive and NOD-like receptor signaling pathways. Functional assays showed that GNG7 overexpression reduced proinflammatory cytokine production, NF-κB p65 phosphorylation, NLRP3 and ASC expression, caspase-1 activation, intracellular ROS accumulation, and neutral-red uptake, whereas GNG7 knockdown produced generally opposite changes. BAY 11-7082 and MCC950 attenuated multiple inflammatory and oxidative changes associated with GNG7 knockdown, supporting the involvement of NF-κB/NLRP3-related signaling. In mice, pulmonary GNG7 knockdown worsened lung injury, changed BALF cytokine levels toward a more inflammatory pattern, and altered CD80/CD206 marker profiles. These findings suggest that GNG7 helps limit Poly I:C induced macrophage inflammation, possibly through NF-κB/NLRP3-related signaling. Further studies are needed before GNG7 can be considered a therapeutic target for ALI.