Butorphanol Promotes Macrophage Phenotypic Transition to Inhibit Inflammatory Lung Injury via κ Receptors
Open Access
- 7 July 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by diffuse inflammation of the lung parenchyma and refractory hypoxemia. Butorphanol is commonly used clinically for perioperative pain relief, but whether butorphanol can regulate LPS-induced alveolar macrophage polarization is unclear. In this study, we observed that butorphanol markedly attenuated sepsis-induced lung tissue injury and mortality in mice. Moreover, butorphanol also decreased the expression of M1 phenotype markers (TNF-α, IL-6, IL-1β and iNOS) and enhanced the expression of M2 marker (CD206) in alveolar macrophages in the bronchoalveolar lavage fluid (BALF) of LPS-stimulated mice. Butorphanol administration reduced LPS-induced numbers of proinflammatory (M1) macrophages and increased numbers of anti-inflammatory (M2) macrophages in the lungs of mice. Furthermore, we found that butorphanol-mediated suppression of the LPS-induced increases in M1 phenotype marker expression (TNF-α, IL-6, IL-1β and iNOS) in bone marrow-derived macrophages (BMDMs), and this effect was reversed by κ-opioid receptor (KOR) antagonists. Moreover, butorphanol inhibited the interaction of TLR4 with MyD88 and further suppressed NF-κB and MAPKs activation. In addition, butorphanol prevented the Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-mediated IFN signaling pathway. These effects were ameliorated by KOR antagonists. Thus, butorphanol may promote macrophage polarization from a proinflammatory to an anti-inflammatory phenotype secondary to the inhibition of NF-κB, MAPKs, and the TRIF-mediated IFN signaling pathway through κ receptors.Keywords
This publication has 52 references indexed in Scilit:
- Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and ImmunityImmunity, 2011
- Transcriptional regulation by STAT6Immunologic Research, 2011
- The Pathogenesis of SepsisAnnual review of pathology, 2011
- Pattern Recognition Receptors and InflammationCell, 2010
- Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor κBProceedings of the National Academy of Sciences of the United States of America, 2009
- Modeling the immune rheostat of macrophages in the lung in response to infectionProceedings of the National Academy of Sciences of the United States of America, 2009
- Alternative Activation of Macrophages: An Immunologic Functional PerspectiveAnnual Review of Immunology, 2009
- Exploring the full spectrum of macrophage activationNature Reviews Immunology, 2008
- Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 productionNature Medicine, 2008