Short-Term Autophagy Preconditioning Upregulates the Expression of COX2 and PGE2 and Alters the Immune Phenotype of Human Adipose-Derived Stem Cells In Vitro

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dc.creatorWise, Rachel M.
dc.creatorAl-Ghadban, Sara
dc.creatorHarrison, Mark A. A.
dc.creatorSullivan, Brianne N.
dc.creatorMonaco, Emily R.
dc.creatorAleman, Sarah J.
dc.creatorDonato, Umberto M.
dc.creatorBunnell, Bruce A.
dc.creator.orcid0000-0001-6196-3722 (Bunnell, Bruce A.)
dc.date.accessioned2022-08-25T15:39:46Z
dc.date.available2022-08-25T15:39:46Z
dc.date.issued2022-04-19
dc.description.abstractHuman adipose-derived stem cells (hASCs) are potent modulators of inflammation and promising candidates for the treatment of inflammatory and autoimmune diseases. Strategies to improve hASC survival and immunoregulation are active areas of investigation. Autophagy, a homeostatic and stress-induced degradative pathway, plays a crucial role in hASC paracrine signaling-a primary mechanism of therapeutic action. Therefore, induction of autophagy with rapamycin (Rapa), or inhibition with 3-methyladenine (3-MA), was examined as a preconditioning strategy to enhance therapeutic efficacy. Following preconditioning, both Rapa and 3-MA-treated hASCs demonstrated preservation of stemness, as well as upregulated transcription of cyclooxygenase-2 (COX2) and interleukin-6 (IL-6). Rapa-ASCs further upregulated TNFalpha-stimulated gene-6 (TSG-6) and interleukin-1 beta (IL-1β), indicating additional enhancement of immunomodulatory potential. Preconditioned cells were then stimulated with the inflammatory cytokine interferon-gamma (IFNγ) and assessed for immunomodulatory factor production. Rapa-pretreated cells, but not 3-MA-pretreated cells, further amplified COX2 and IL-6 transcripts following IFNγ exposure, and both groups upregulated secretion of prostaglandin-E2 (PGE2), the enzymatic product of COX2. These findings suggest that a 4-h Rapa preconditioning strategy may bestow the greatest improvement to hASC expression of cytokines known to promote tissue repair and regeneration and may hold promise for augmenting the therapeutic potential of hASCs for inflammation-driven pathological conditions.
dc.description.sponsorshipThe funds used for these studies were private funds from Tulane University.
dc.identifier.citationWise, R. M., Al-Ghadban, S., Harrison, M., Sullivan, B. N., Monaco, E. R., Aleman, S. J., Donato, U. M., & Bunnell, B. A. (2022). Short-Term Autophagy Preconditioning Upregulates the Expression of COX2 and PGE2 and Alters the Immune Phenotype of Human Adipose-Derived Stem Cells In Vitro. Cells, 11(9), 1376. https://doi.org/10.3390/cells11091376
dc.identifier.issn2073-4409
dc.identifier.issue9
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31650
dc.identifier.volume11
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/cells11091376
dc.rights.holder© 2022 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCells
dc.subject3-methyladenine
dc.subjectadipose tissue-derived stem cells (ASCs)
dc.subjectimmunosuppression
dc.subjectinflammation
dc.subjectrapamycin
dc.subject.meshAdipose Tissue
dc.subject.meshAutophagy
dc.subject.meshCyclooxygenase 2 / metabolism
dc.subject.meshCytokines / metabolism
dc.subject.meshDinoprostone / metabolism
dc.subject.meshHumans
dc.subject.meshInflammation / metabolism
dc.subject.meshInterferon-gamma / metabolism
dc.subject.meshInterleukin-6 / metabolism
dc.subject.meshMesenchymal Stem Cells / metabolism
dc.subject.meshPhenotype
dc.subject.meshSirolimus
dc.titleShort-Term Autophagy Preconditioning Upregulates the Expression of COX2 and PGE2 and Alters the Immune Phenotype of Human Adipose-Derived Stem Cells In Vitro
dc.typeArticle
dc.type.materialtext

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