PMID- 38333754 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240210 IS - 2008-3866 (Print) IS - 2008-3874 (Electronic) IS - 2008-3866 (Linking) VI - 27 IP - 3 DP - 2024 TI - Therapeutic potential of HUC-MSC-exos primed with IFN-gamma against LPS-induced acute lung injury. PG - 375-382 LID - 10.22038/IJBMS.2023.74372.16156 [doi] AB - OBJECTIVES: Human umbilical cord mesenchymal stem cells (HUC-MSCs) are pluripotent stem cells with anti-inflammatory and immunomodulatory properties used in the treatment of acute lung injury (ALI). However, the treatment of ALI using exosomes derived from HUC-MSCs (HUC-MSC-exos) primed with interferon-gamma (IFN-gamma-exos) has not been described. This study investigated the effects of IFN-gamma-exos on ALI. MATERIALS AND METHODS: IFN-gamma primed and unprimed HUC-MSC-exos (IFN-gamma-exos and CON-exos, respectively) were extracted, identified, and traced. A549 cells and mice subjected to lipopolysaccharide (LPS)-induced inflammation were treated with IFN-gamma-exos or CON-exos. Viability; interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and reactive oxygen species (ROS) levels; NF-kappaB p65, and NLRP3 expression and histology and lung injury scores were measured in cell, supernatant or lung tissue. RESULTS: Indoleamine 2,3-dioxygenase (IDO) mRNA expression was elevated in HUC-MSCs primed with 5 ng/mL IFN-gamma (P<0.001), and IFN-gamma-exos and CON-exos were successfully extracted. LPS-induced inflammation resulted in decreased cell viability in A549 cells, and increased IL-1beta, IL-6, TNF-alpha and ROS levels and NF-kappaB p65 and NLRP3 expression in A549 cells and mice(P<0.05 to P<0.001). Treatment with IFN-gamma-exos and CON-exos increased cell viability and decreased the concentrations of IL-1beta, and ROS, expression of NF-kappaB p65 and NLRP3, and the lung injury score, and these effects were more obvious for IFN-gamma-exos(P<0.05 to P<0.001). CONCLUSION: IFN-gamma-exos reduced oxidative stress and inflammatory responses in LPS-induced A549 cells and mice. The result demonstrated the therapeutic potential of IFN-gamma-exos in LPS-induced ALI. FAU - Wang, Chun AU - Wang C AD - Kunming Medical University, Kunming, China. AD - Department of Emergency Intensive Care Unit, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China. FAU - Jiang, Chen AU - Jiang C AD - Kunming Medical University, Kunming, China. FAU - Yang, Yiran AU - Yang Y AD - Kunming Medical University, Kunming, China. FAU - Xi, Cheng AU - Xi C AD - Department of Gastrointestinal Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China. FAU - Yin, Yunxiang AU - Yin Y AD - Department of Emergency Intensive Care Unit, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China. FAU - Wu, Haiying AU - Wu H AD - Department of Emergency, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China. FAU - Qian, Chuanyun AU - Qian C AD - Department of Emergency, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China. LA - eng PT - Journal Article PL - Iran TA - Iran J Basic Med Sci JT - Iranian journal of basic medical sciences JID - 101517966 PMC - PMC10849211 OTO - NOTNLM OT - Acute lung injury OT - Exosomes OT - Inflammation OT - Interferon gamma OT - Mesenchymal stem cells COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/02/09 06:43 MHDA- 2024/02/09 06:44 PMCR- 2024/01/01 CRDT- 2024/02/09 04:09 PHST- 2023/08/15 00:00 [received] PHST- 2023/10/30 00:00 [accepted] PHST- 2024/02/09 06:44 [medline] PHST- 2024/02/09 06:43 [pubmed] PHST- 2024/02/09 04:09 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.22038/IJBMS.2023.74372.16156 [doi] PST - ppublish SO - Iran J Basic Med Sci. 2024;27(3):375-382. doi: 10.22038/IJBMS.2023.74372.16156.