ADSC-Conditioned Medium Mitigates LPS-Induced Acute Lung Injury by Inhibiting Alveolar Macrophage Pyroptosis

TL;DR

This study shows that a cell-free treatment derived from fat cells can reduce lung inflammation and injury in rats by preventing a specific type of immune cell death.

Contribution

The study reveals that ADSC-CM mitigates ALI by inhibiting alveolar macrophage pyroptosis through TLR4/MyD88/NF-κB and NLRP3 pathways.

Findings

ADSC-CM reduced lung damage and systemic inflammation in LPS-induced ALI in rats.

ADSC-CM inhibited pyroptosis in alveolar macrophages via suppression of TLR4/MyD88/NF-κB and NLRP3 pathways.

Downregulation of TLR4 was a key mechanism behind the protective effects of ADSC-CM.

Abstract

Acute lung injury (ALI) is characterized by overwhelming pulmonary inflammation and high mortality, yet specific pharmacological interventions remain critically limited. Adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) represents a novel cell-free strategy with substantial therapeutic potential. This study investigated the protective effects of ADSC-CM in a rat model of lipopolysaccharide (LPS)-induced ALI. Systemic administration of ADSC-CM significantly attenuated pulmonary pathological damage, reduced systemic inflammatory cytokine levels, and inhibited pyroptosis within lung tissues. Mechanistically, in vitro studies using the NR8383 alveolar macrophage (AM) cell line revealed that ADSC-CM suppressed the TLR4/MyD88/NF-κB signaling axis and the NLRP3/Caspase-1/GSDMD-mediated pyroptotic cascade. These effects were primarily driven by the downregulation of TLR4 expression, although additional molecular targets likely contribute to this protective profile. Our findings highlight the therapeutic efficacy of ADSC-CM in modulating pyroptosis and inflammatory responses in AMs, providing a robust mechanistic rationale for developing ADSC-CM as a cell-free therapeutic platform for the management of ALI.

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