論文 - 詳細
| RRC ID | 45166 |
|---|---|
| 著者 | Wen L, Zhu M, Madigan MC, You J, King NJ, Billson FA, McClellan K, Sutton G, Petsoglou C. |
| タイトル | Immunomodulatory effects of bone marrow-derived mesenchymal stem cells on pro-inflammatory cytokine-stimulated human corneal epithelial cells. |
| ジャーナル | PLoS One |
| Abstract |
PURPOSE:To investigate the modulatory effect of rat bone marrow mesenchymal stem cells (MSC) on human corneal epithelial cells (HCE-T) stimulated with pro-inflammatory cytokines interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in an in vitro co-cultured model. METHODS:HCE-T alone and co-cultured with MSC were stimulated with IFN-γ/TNF for 24 and 48 hours or left untreated. The expression of intracellular adhesion molecule (ICAM)-1, human leukocyte antigen ABC, DR and G (HLA-ABC, HLA-DR, HLA-G) were investigated by flow cytometry. Subcellular localization of nuclear factor-kappa B (NF-κB) and expression of indoleamine 2,3-dioxygenase (IDO) were assessed by immunofluorescence staining and western blot. The concentration of transforming growth factor beta 1 (TGF-β1) in the conditioned media from different cultures was evaluated by enzyme-linked immunosorbent assay. NF-κB and TGF-β1 signaling pathway blocking experiments were performed to analyze associations between the expression of cell surface molecules and the NF-κB transcription pathway, and the expression of IDO and TGF-β1 signaling pathway. RESULTS:IFN-γ/TNF treatment significantly up-regulated expression of ICAM-1, HLA-ABC, and induced de novo expression of HLA-DR and IDO on HCE-T cultured alone, while HLA-G expression remained unaffected. Up-regulation was significantly inhibited by co-culture with MSC. Increased TGF-β1 secretion was detected in 48 h IFN-γ/TNF-stimulated MSC monocultures and HCE-T/MSC co-cultures. MSC attenuated the activation of cytokine-induced NF-κB and IDO induction. Blockade of NF-κB transcription pathway by BMS-345541 significantly reduced the up-regulation of ICAM-1, HLA-ABC, HLA-DR and IDO expression, while blockade of TGF-β1 signaling pathways reversed the modulatory effect of MSC on IDO expression. CONCLUSIONS:MSC reduced the expression of adhesion and immunoregulatory molecules on pro-inflammatory cytokine-stimulated HCE-T via the NF-κB transcription pathway. MSC attenuated expression of IDO through both NF-κB transcription and TGF-β1 signaling pathways. Co-culture of HCEC with MSC therefore provides a useful in vitro model to study the anti-inflammatory properties of MSC on corneal epithelium. |
| 巻・号 | 9(7) |
| ページ | e101841 |
| 公開日 | 2014-1-1 |
| DOI | 10.1371/journal.pone.0101841 |
| PII | PONE-D-14-11355 |
| PMID | 25003339 |
| PMC | PMC4086952 |
| MeSH | Animals Cell Adhesion Molecules / metabolism Cell Line, Transformed Cytokines / pharmacology* Enzyme Activation Epithelial Cells / drug effects* Epithelial Cells / immunology Epithelial Cells / metabolism* Epithelium, Corneal / cytology Epithelium, Corneal / drug effects* Epithelium, Corneal / immunology Epithelium, Corneal / metabolism* Humans Immunomodulation Immunophenotyping Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism Inflammation Mediators / pharmacology* Mesenchymal Stem Cells / immunology Mesenchymal Stem Cells / metabolism* NF-kappa B / metabolism Phenotype Protein Transport Rats Transforming Growth Factor beta1 / metabolism |
| IF | 2.74 |
| 引用数 | 16 |
| WOS 分野 | OPHTHALMOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HCE-T(RCB2280) |