Emodin attenuates severe acute pancreatitis- associated acute lung injury by suppressing pancreatic exosome-mediated alveolar macrophage activation

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) is a serious disease associ-ated with high mortality. Emodin has been applied to alleviate SAP-ALI; however, the mechanism re-mains unclear. We report that the therapeutic role of emodin in attenuating SAP-AL I is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely, emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exo-somes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exo-somes. In detail, emodin-primed exosomes suppressed the NF-kB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARg pathway, while these ef-fects were amplified/abolished by PPARg agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflamma-tion. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury, and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.(c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).