Suppression of IL-10 production by activated B cells via a cell contact-dependent cyclooxygenase-2 pathway upregulated in IFN-γ-treated mesenchymal stem cells

Heřmánková, Barbora; Zajı́cová, Alena; Javorková, Eliška; Chudíčková, Milada; Trošan, Peter; Hájková, Michaela; Krulová, Magdaléna; Holáň, Vladimı́r

doi:10.1016/j.imbio.2015.09.017

Cited by 37 publications

(27 citation statements)

References 38 publications

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“…For example, direct MSC contact with CD4+ cells required to induce CD4 + CD25 + FoxP3 + Treg cells, which was followed by increased expression of TGF‐β1 and PGE2 . When MSCs were exposed to pro‐inflammatory cytokines such as IFNγ and TNFα, they became activated and modulated IL‐10 production by B cells through a contact‐dependent mechanism . IFNγ was required to initiate MSC efficacy and is known to enhance the immunosuppressive properties of MSCs .…”

Section: Discussionmentioning

confidence: 99%

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

et al. 2016

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Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone-seeking compound, LLP2A-Alendronate (LLP2A-Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A-Ale or a combination of LLP2A-Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid-femur fracture was induced in two-month-old osterix-mCherry (Osx-mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A-Ale (500 µg/kg, IV), MSCs derived from wild-type female Osx-mCherry adipose tissue (ADSC, 3 × 105, IV) or ADSC + LLP2A-Ale. In phosphate buffered saline-treated mice, females had higher systemic and surface-based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A-Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex-independent. There was a sex-difference in the rate of fracture healing. ADSC and LLP2A-Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

et al. 2016

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“…However, they did not report the secretion of PEG2 in IFN‐γ‐treated MSCs. They found only IL‐10 production by exogenous PGE2 and showed that IL‐10 production produced is inhibited by the COX2 inhibitor INDO (Hermankova et al, ). We finally found that cotreatment of hUCB‐MSCs with IFN‐γ and IL‐1β showed higher expression levels of PGE2 and COX2 when compared with the single‐treated hUCB‐MSCs, respectively.…”

Section: Discussionmentioning

confidence: 99%

Preconditioning with interleukin‐1 beta and interferon‐gamma enhances the efficacy of human umbilical cord blood‐derived mesenchymal stem cells‐based therapy via enhancing prostaglandin E2 secretion and indoleamine 2,3‐dioxygenase activity in dextran sulfate sodium‐induced colitis

Yoo

Park

et al. 2019

J Tissue Eng Regen Med

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Preconditioning with inflammatory cytokines has improved mesenchymal stem cells characteristics, including differentiation and immunomodulating functions. In this study, we developed a preconditioning combination strategy using interleukin‐1beta (IL‐1β) and interferon‐gamma (IFN‐γ) to enhance the immuneregulatory ability of human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs). Our results showed that hUCB‐MSCs preconditioned with IL‐1β and IFN‐γ (primed hUCB‐MSCs) created a statistically significant decrease in peripheral blood mononuclear cell proliferation, indicating that their immunosuppressive ability was increased. The secretion of PGE2, cyclooxygenase 2 mRNA expression, and indoleamine 2,3‐dioxygenase (IDO) mRNA expression in primed hUCB‐MSCs was significantly higher than those in the untreated hUCB‐MSCs or the IL‐1β or IFN‐γ only treated hUCB‐MSCs. When inhibitors of IDO and PGE2 were treated, peripheral blood mononuclear cell proliferation, which is inhibited by primed hUCB‐MSCs, was recovered. We found that Th1 T cell differentiation was also inhibited by PGE2 and IDO in the primed hUCB‐MSCs, and Tregs differentiation was increased by PGE2 and IDO in the primed hUCB‐MSCs. Furthermore, the primed hUCB‐MSCs as well as supernatants increase CD4+ T cells migration. We demonstrated the therapeutic effects of primed hUCB‐MSCs in dextran sulfate sodium‐induced colitis model. In conclusion, we have demonstrated that primed hUCB‐MSCs simultaneously enhance PGE2 and IDO and greatly improve the immunoregulatory capacity of MSCs, and we have developed an optimal condition for pretreatment of MSCs for the treatment of immune diseases. Our results raise the possibility that the combination of PGE2 and IDO could be therapeutic mediators for controlling immunosuppression of MSCs.

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“…However, contact-dependent and soluble factor-mediated mechanisms are not mutually exclusive, as the release of soluble immunoregulatory molecules by MSCs might also require contact between MSCs and their target cells. In this context, Hermankova et al reported previously that IFN-g-treated MSCs suppress IL-10 production from activated B cells by a mechanism requiring cell contact and Cox-2 pathway activation [36].…”

Section: Inhibition Of Pdc Generation By Msc Is Contact-dependentmentioning

confidence: 99%

Contact-dependent abrogation of bone marrow-derived plasmacytoid dendritic cell differentiation by murine mesenchymal stem cells

Hackstein

Tschipakow

Bein

et al. 2016

Biochemical and Biophysical Research Communications

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Suppression of IL-10 production by activated B cells via a cell contact-dependent cyclooxygenase-2 pathway upregulated in IFN-γ-treated mesenchymal stem cells

Cited by 37 publications

References 38 publications

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

Preconditioning with interleukin‐1 beta and interferon‐gamma enhances the efficacy of human umbilical cord blood‐derived mesenchymal stem cells‐based therapy via enhancing prostaglandin E2 secretion and indoleamine 2,3‐dioxygenase activity in dextran sulfate sodium‐induced colitis

Contact-dependent abrogation of bone marrow-derived plasmacytoid dendritic cell differentiation by murine mesenchymal stem cells

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