{"title":"LPS-Induced Intracellular Complement 3 Activation Regulated ATP Production in Yak Rumen Epithelial Cells.","authors":"Qiang Han, Qiqi Zhang, Duoting Wu, Zihan Yang, Jinyang Huang, Zhisheng Wang, Huawei Zou, Quanhui Peng, Yukun Meng, Yahui Jiang, Jianxin Xiao, Rui Hu","doi":"10.3390/vetsci12090841","DOIUrl":null,"url":null,"abstract":"<p><p>This study aimed to investigate whether intracellular complement 3 (C3) activation regulates ATP production in yak rumen epithelial cells under inflammatory conditions and its potential mechanism. An in vitro inflammation model was established by stimulating yak rumen epithelial cells with lipopolysaccharide (LPS). Then, protease inhibitors targeting C3 activation enzymes were added. Additionally, to explore the downstream signaling pathway, exogenous C3a and the C3a receptor (C3aR) inhibitor C3aRY were applied to the inflammation model. After treatment with different concentrations of LPS, the gene expression levels and concentrations of pro-inflammatory cytokines, such as <i>TNF-α</i>, <i>IL-1β</i>, and <i>IL-6</i> were significantly up-regulated (<i>p</i> < 0.05), while a significant reduction in cellular ATP levels was observed (<i>p</i> < 0.05), along with a significant reduction in mitochondrial membrane potential (<i>p</i> < 0.05). After treating the inflammation model with different protease inhibitors, the ATP content and gene expression of the ATP synthase subunit <i>ATP5A</i> were significantly increased (<i>p</i> < 0.05). Exogenous addition of the C3aR inhibitor C3aRY in the inflammation model exhibited a significant increase in ATP content and <i>ATP5A</i> gene expression (<i>p</i> < 0.05) when compared to the inflammation model. These results demonstrated that intracellular C3 activation inhibited ATP production in yak rumen epithelial cells under inflammatory conditions, likely through C3a-C3aR signaling and the cAMP/PKA pathway.</p>","PeriodicalId":23694,"journal":{"name":"Veterinary Sciences","volume":"12 9","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474471/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary Sciences","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.3390/vetsci12090841","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
This study aimed to investigate whether intracellular complement 3 (C3) activation regulates ATP production in yak rumen epithelial cells under inflammatory conditions and its potential mechanism. An in vitro inflammation model was established by stimulating yak rumen epithelial cells with lipopolysaccharide (LPS). Then, protease inhibitors targeting C3 activation enzymes were added. Additionally, to explore the downstream signaling pathway, exogenous C3a and the C3a receptor (C3aR) inhibitor C3aRY were applied to the inflammation model. After treatment with different concentrations of LPS, the gene expression levels and concentrations of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6 were significantly up-regulated (p < 0.05), while a significant reduction in cellular ATP levels was observed (p < 0.05), along with a significant reduction in mitochondrial membrane potential (p < 0.05). After treating the inflammation model with different protease inhibitors, the ATP content and gene expression of the ATP synthase subunit ATP5A were significantly increased (p < 0.05). Exogenous addition of the C3aR inhibitor C3aRY in the inflammation model exhibited a significant increase in ATP content and ATP5A gene expression (p < 0.05) when compared to the inflammation model. These results demonstrated that intracellular C3 activation inhibited ATP production in yak rumen epithelial cells under inflammatory conditions, likely through C3a-C3aR signaling and the cAMP/PKA pathway.
期刊介绍:
Veterinary Sciences is an international and interdisciplinary scholarly open access journal. It publishes original that are relevant to any field of veterinary sciences, including prevention, diagnosis and treatment of disease, disorder and injury in animals. This journal covers almost all topics related to animal health and veterinary medicine. Research fields of interest include but are not limited to: anaesthesiology anatomy bacteriology biochemistry cardiology dentistry dermatology embryology endocrinology epidemiology genetics histology immunology microbiology molecular biology mycology neurobiology oncology ophthalmology parasitology pathology pharmacology physiology radiology surgery theriogenology toxicology virology.