Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides

Purpose: At present, therapeutic interventions to treat acute lung injury (ALI) remain largely limited to lung-protective strategies, as no real molecular-driven therapeutic intervention has yet become available. The administration of bacterial lipopolysaccharides (LPS) is known as an inflammatory a...

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Main Authors: Ika Adhani Sholihah, Anggraini Barlian
Format: Article
Language:English
Published: Tabriz University of Medical Sciences 2024-07-01
Series:Advanced Pharmaceutical Bulletin
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Online Access:https://apb.tbzmed.ac.ir/PDF/apb-14-434.pdf
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author Ika Adhani Sholihah
Anggraini Barlian
author_facet Ika Adhani Sholihah
Anggraini Barlian
author_sort Ika Adhani Sholihah
collection DOAJ
description Purpose: At present, therapeutic interventions to treat acute lung injury (ALI) remain largely limited to lung-protective strategies, as no real molecular-driven therapeutic intervention has yet become available. The administration of bacterial lipopolysaccharides (LPS) is known as an inflammatory activator, representing a frequently used model of ALI. This study investigated the biological function of normoxic (21% O2 ) vs. hypoxic conditions (5% O2 ) obtained from human Wharton’s Jelly mesenchymal stem cells (hWJ-MSCs) and discovered that exosomes have the ability to suppress inflammatory responses by specifically targeting TNF-α, IL-1β, IL-6. and identify the toll-like receptor 4 (TLR4) NF-κβ gene expression. Methods: Primer culture hWJ-MSCs characterization with trilineage differentiation and CD markers was conducted. To obtain exosomes, hWJ-MSCs were stimulated with two different oxygen levels: 21% (nor-exo) and 5% (hypo-exo). Then, the L2 cell line was induced with LPS 1 µg/mL. Inflamed-L2 was treated with nor-exo, hypo-exo, and dexamethasone as a positive control. The RNA extracted from treated L2 cells was utilized to examine the gene expression profiles of TLR4 and NF-κβ, and the medium was used to measure tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 levels using ELISA. Lastly, proteomic analysis of the exosome using LC/MS-MS was conducted. Results: Nor-exo and hypo-exo can be characterized and can produce higher yields exosomes under hypoxic conditions. The expression of TLR4 and NF-κβ genes and the proinflammatory levels such as IL-6, IL-1β, and TNF-α levels in nor-exo and hypo-exo treatments decreased. Conclusion: Nor-exo and hypo-exo derived from hWJ-MSCs were proven to have anti-inflammatory activities.
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spelling doaj-art-e7a6cebff1ea4d40a67ed2ba9cf289912025-08-20T02:52:24ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082024-07-0114243444410.34172/apb.2024.027apb-41950Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by LipopolysaccharidesIka Adhani Sholihah0Anggraini Barlian1School of Life Sciences and Technology, Institut Teknologi Bandung, Jl. Ganesha No.10, Bandung 40132, Indonesia.School of Life Sciences and Technology, Institut Teknologi Bandung, Jl. Ganesha No.10, Bandung 40132, Indonesia.Purpose: At present, therapeutic interventions to treat acute lung injury (ALI) remain largely limited to lung-protective strategies, as no real molecular-driven therapeutic intervention has yet become available. The administration of bacterial lipopolysaccharides (LPS) is known as an inflammatory activator, representing a frequently used model of ALI. This study investigated the biological function of normoxic (21% O2 ) vs. hypoxic conditions (5% O2 ) obtained from human Wharton’s Jelly mesenchymal stem cells (hWJ-MSCs) and discovered that exosomes have the ability to suppress inflammatory responses by specifically targeting TNF-α, IL-1β, IL-6. and identify the toll-like receptor 4 (TLR4) NF-κβ gene expression. Methods: Primer culture hWJ-MSCs characterization with trilineage differentiation and CD markers was conducted. To obtain exosomes, hWJ-MSCs were stimulated with two different oxygen levels: 21% (nor-exo) and 5% (hypo-exo). Then, the L2 cell line was induced with LPS 1 µg/mL. Inflamed-L2 was treated with nor-exo, hypo-exo, and dexamethasone as a positive control. The RNA extracted from treated L2 cells was utilized to examine the gene expression profiles of TLR4 and NF-κβ, and the medium was used to measure tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 levels using ELISA. Lastly, proteomic analysis of the exosome using LC/MS-MS was conducted. Results: Nor-exo and hypo-exo can be characterized and can produce higher yields exosomes under hypoxic conditions. The expression of TLR4 and NF-κβ genes and the proinflammatory levels such as IL-6, IL-1β, and TNF-α levels in nor-exo and hypo-exo treatments decreased. Conclusion: Nor-exo and hypo-exo derived from hWJ-MSCs were proven to have anti-inflammatory activities.https://apb.tbzmed.ac.ir/PDF/apb-14-434.pdfanti-inflammatoryexosomeshypoxiainterleukin-1βhwj-mscstumor necrosis factor α
spellingShingle Ika Adhani Sholihah
Anggraini Barlian
Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides
Advanced Pharmaceutical Bulletin
anti-inflammatory
exosomes
hypoxia
interleukin-1β
hwj-mscs
tumor necrosis factor α
title Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides
title_full Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides
title_fullStr Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides
title_full_unstemmed Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides
title_short Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides
title_sort anti inflammatory potency of human wharton s jelly mesenchymal stem cell derived exosomes on l2 cell line induced by lipopolysaccharides
topic anti-inflammatory
exosomes
hypoxia
interleukin-1β
hwj-mscs
tumor necrosis factor α
url https://apb.tbzmed.ac.ir/PDF/apb-14-434.pdf
work_keys_str_mv AT ikaadhanisholihah antiinflammatorypotencyofhumanwhartonsjellymesenchymalstemcellderivedexosomesonl2celllineinducedbylipopolysaccharides
AT anggrainibarlian antiinflammatorypotencyofhumanwhartonsjellymesenchymalstemcellderivedexosomesonl2celllineinducedbylipopolysaccharides