Lactate attenuates PANoptosis and enhances ZBP-1 lactylation in macrophages in acute lung injury.

ABSTRACT:

Introduction

Acute lung injury (ALI), characterized by excessive inflammation and cell death, is closely associated with ZBP1-mediated PANoptosis, a programmed cell death mechanism. The intrinsic regulatory mechanism of PANoptosis remains poorly investigated.

Methods

In this study, we investigated the protective effects of lactate on lipopolysaccharide (LPS)-induced ALI and its potential regulatory role in ZBP1-mediated PANoptosis.

Results

Our results showed that lactate effectively reduced inflammatory cytokine (TNF-α, IL-6, and IL-1β) and CD11b⁺Gr1⁺ monocyte infiltration in bronchoalveolar lavage fluid and serum. It also alleviated lung pathology and suppressed PANoptosis markers (cleaved caspase-1, GSDMD-p20, phospho-MLKL, and cleaved caspase-

SUBMITTER: Wang D 

PROVIDER: S-EPMC12754177 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature