000120679 001__ 120679
000120679 005__ 20251203113955.0
000120679 0247_ $$2doi$$a10.3389/fimmu.2017.00479
000120679 0247_ $$2pmid$$apmid:28553282
000120679 0247_ $$2pmc$$apmc:PMC5425596
000120679 0247_ $$2altmetric$$aaltmetric:20695757
000120679 037__ $$aDKFZ-2017-01105
000120679 041__ $$aeng
000120679 082__ $$a610
000120679 1001_ $$aLerrer, Shalom$$b0
000120679 245__ $$aCo-Inflammatory Roles of TGFβ1 in the Presence of TNFα Drive a Pro-inflammatory Fate in Mesenchymal Stem Cells.
000120679 260__ $$aLausanne$$bFrontiers Media$$c2017
000120679 3367_ $$2DRIVER$$aarticle
000120679 3367_ $$2DataCite$$aOutput Types/Journal article
000120679 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1764758381_1331671
000120679 3367_ $$2BibTeX$$aARTICLE
000120679 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000120679 3367_ $$00$$2EndNote$$aJournal Article
000120679 500__ $$a#DKFZ-MOST-Ca187#
000120679 520__ $$aHigh plasticity is a hallmark of mesenchymal stem cells (MSCs), and as such, their differentiation and activities may be shaped by factors of their microenvironment. Bones, tumors, and cardiomyopathy are examples of niches and conditions that contain MSCs and are enriched with tumor necrosis factor α (TNFα) and transforming growth factor β1 (TGFβ1). These two cytokines are generally considered as having opposing roles in regulating immunity and inflammation (pro- and anti-inflammatory, respectively). Here, we performed global gene expression analysis of human bone marrow-derived MSCs and identified overlap in half of the transcriptional programs that were modified by TNFα and TGFβ1. The two cytokines elevated the mRNA expression of soluble factors, including mRNAs of pro-inflammatory mediators. Accordingly, the typical pro-inflammatory factor TNFα prominently induced the protein expression levels of the pro-inflammatory mediators CCL2, CXCL8 (IL-8), and cyclooxygenase-2 (Cox-2) in MSCs, through the NF-κB/p65 pathway. In parallel, TGFβ1 did not elevate CXCL8 protein levels and induced the protein expression of CCL2 at much lower levels than TNFα; yet, TGFβ1 readily induced Cox-2 and acted predominantly via the Smad3 pathway. Interestingly, combined stimulation of MSCs by TNFα + TGFβ1 led to a cooperative induction of all three inflammatory mediators, indicating that TGFβ1 functioned as a co-inflammatory cytokine in the presence of TNFα. The cooperative activities of TNFα + TGFβ1 that have led to CCL2 and CXCL8 induction were almost exclusively dependent on p65 activation and were not regulated by Smad3 or by the upstream regulator TGFβ-activated kinase 1 (TAK1). In contrast, the TNFα + TGFβ1-induced cooperative elevation in Cox-2 was mostly dependent on Smad3 (demonstrating cooperativity with activated NF-κB) and was partly regulated by TAK1. Studies with MSCs activated by TNFα + TGFβ1 revealed that they release factors that can affect other cells in their microenvironment and induce breast tumor cell elongation, migration, and scattering out of spheroid tumor masses. Thus, our findings demonstrate a TNFα + TGFβ1-driven pro-inflammatory fate in MSCs, identify specific molecular mechanisms involved, and propose that TNFα + TGFβ1-stimulated MSCs influence the tumor niche. These observations suggest key roles for the microenvironment in regulating MSC functions, which in turn may affect different health-related conditions.
000120679 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0
000120679 588__ $$aDataset connected to CrossRef, PubMed,
000120679 7001_ $$aLiubomirski, Yulia$$b1
000120679 7001_ $$0P:(DE-He78)3e240c9d490f382fa6be5fcdbcd4056b$$aBott, Alexander$$b2$$udkfz
000120679 7001_ $$0P:(DE-He78)5d2368e14d05ccf8ea8825d5cf8ab1bc$$aAbnaof, Khalid Ali$$b3$$udkfz
000120679 7001_ $$aOren, Nino$$b4
000120679 7001_ $$0P:(DE-HGF)0$$aYousaf, Afsheen$$b5
000120679 7001_ $$0P:(DE-He78)a2dde36c70db0249408e1d88843d17a9$$aKörner, Cindy$$b6$$udkfz
000120679 7001_ $$aMeshel, Tsipi$$b7
000120679 7001_ $$0P:(DE-He78)f6bebe05e7a748d3cbf9f59659567d52$$aWiemann, Stefan$$b8$$udkfz
000120679 7001_ $$aBen-Baruch, Adit$$b9
000120679 773__ $$0PERI:(DE-600)2606827-8$$a10.3389/fimmu.2017.00479$$gVol. 8, p. 479$$p479$$tFrontiers in immunology$$v8$$x1664-3224$$y2017
000120679 909CO $$ooai:inrepo02.dkfz.de:120679$$pVDB
000120679 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)3e240c9d490f382fa6be5fcdbcd4056b$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000120679 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)5d2368e14d05ccf8ea8825d5cf8ab1bc$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000120679 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000120679 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a2dde36c70db0249408e1d88843d17a9$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ
000120679 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f6bebe05e7a748d3cbf9f59659567d52$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000120679 9131_ $$0G:(DE-HGF)POF3-312$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunctional and structural genomics$$x0
000120679 9141_ $$y2017
000120679 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bFRONT IMMUNOL : 2015
000120679 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000120679 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000120679 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000120679 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal
000120679 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ
000120679 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ
000120679 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000120679 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000120679 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000120679 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bFRONT IMMUNOL : 2015
000120679 9201_ $$0I:(DE-He78)B050-20160331$$kB050$$lB050 Molekulare Genomanalyse$$x0
000120679 980__ $$ajournal
000120679 980__ $$aVDB
000120679 980__ $$aI:(DE-He78)B050-20160331
000120679 980__ $$aUNRESTRICTED