Kyeongbo Kim, Ju-Hyun An, Su-Min Park, GaHyun Lim, Kyung-Won Seo, Hwa-Young Youn
{"title":"猫脂肪组织间充质干细胞在 TNF-α 刺激下通过 COX-2/PGE2 激活改善 DSS 引起的小鼠结肠炎。","authors":"Kyeongbo Kim, Ju-Hyun An, Su-Min Park, GaHyun Lim, Kyung-Won Seo, Hwa-Young Youn","doi":"10.4142/jvs.23106","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals.</p><p><strong>Objectives: </strong>This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model.</p><p><strong>Methods: </strong>Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b<sup>+</sup>CD206<sup>+</sup> macrophages than in the other groups. <i>In vitro</i>, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells.</p><p><strong>Conclusions: </strong>These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE<sub>2</sub> pathway.</p>","PeriodicalId":17557,"journal":{"name":"Journal of Veterinary Science","volume":"24 4","pages":"e52"},"PeriodicalIF":1.5000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/a1/jvs-24-e52.PMC10404709.pdf","citationCount":"0","resultStr":"{\"title\":\"Amelioration of DSS-induced colitis in mice by TNF-α-stimulated mesenchymal stem cells derived from feline adipose tissue via COX-2/PGE<sub>2</sub> activation.\",\"authors\":\"Kyeongbo Kim, Ju-Hyun An, Su-Min Park, GaHyun Lim, Kyung-Won Seo, Hwa-Young Youn\",\"doi\":\"10.4142/jvs.23106\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals.</p><p><strong>Objectives: </strong>This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model.</p><p><strong>Methods: </strong>Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b<sup>+</sup>CD206<sup>+</sup> macrophages than in the other groups. <i>In vitro</i>, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells.</p><p><strong>Conclusions: </strong>These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE<sub>2</sub> pathway.</p>\",\"PeriodicalId\":17557,\"journal\":{\"name\":\"Journal of Veterinary Science\",\"volume\":\"24 4\",\"pages\":\"e52\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/a1/jvs-24-e52.PMC10404709.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Veterinary Science\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.4142/jvs.23106\",\"RegionNum\":3,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Veterinary Science","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.4142/jvs.23106","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
Amelioration of DSS-induced colitis in mice by TNF-α-stimulated mesenchymal stem cells derived from feline adipose tissue via COX-2/PGE2 activation.
Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals.
Objectives: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model.
Methods: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.
Results: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b+CD206+ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells.
Conclusions: These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE2 pathway.
期刊介绍:
The Journal of Veterinary Science (J Vet Sci) is devoted to the advancement and dissemination of scientific knowledge concerning veterinary sciences and related academic disciplines. It is an international journal indexed in the Thomson Scientific Web of Science, SCI-EXPANDED, Sci Search, BIOSIS Previews, Biological Abstracts, Focus on: Veterinary Science & Medicine, Zoological Record, PubMed /MEDLINE, Index Medicus, Pubmed Central, CAB Abstracts / Index Veterinarius, EBSCO, AGRIS and AGRICOLA. This journal published in English by the Korean Society of Veterinary Science (KSVS) being distributed worldwide.