دورية أكاديمية
Minocycline modulates NFκB phosphorylation and enhances antimicrobial activity against Staphylococcus aureus in mesenchymal stromal/stem cells.
| العنوان: | Minocycline modulates NFκB phosphorylation and enhances antimicrobial activity against Staphylococcus aureus in mesenchymal stromal/stem cells. |
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| المؤلفون: | Guerra AD; School of Pharmacy, Division of Pharmaceutical Sciences, Pharmacy Practice Division, University of Wisconsin-Madison, 777 Highland Avenue, 7123 Rennebohm Hall, Madison, WI, 53705, USA., Rose WE; School of Pharmacy, Division of Pharmaceutical Sciences, Pharmacy Practice Division, University of Wisconsin-Madison, 777 Highland Avenue, 7123 Rennebohm Hall, Madison, WI, 53705, USA., Hematti P; School of Medicine and Public Health, Department of Medicine, Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, 1685 Highland Avenue, Madison, WI, 53705, USA., Kao WJ; School of Pharmacy, Division of Pharmaceutical Sciences, Pharmacy Practice Division, University of Wisconsin-Madison, 777 Highland Avenue, 7123 Rennebohm Hall, Madison, WI, 53705, USA. WJKao@wisc.edu.; College of Engineering, Department of Biomedical Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, WI, 53706, USA. WJKao@wisc.edu.; School of Medicine and Public Health, Department of Surgery, University of Wisconsin-Madison, 1685 Highland Avenue, Madison, WI, 53705, USA. WJKao@wisc.edu.; Present Address: 10/F Knowles Building, Pokfulam, Hong Kong. WJKao@wisc.edu. |
| المصدر: | Stem cell research & therapy [Stem Cell Res Ther] 2017 Jul 21; Vol. 8 (1), pp. 171. Date of Electronic Publication: 2017 Jul 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101527581 Publication Model: Electronic Cited Medium: Internet ISSN: 1757-6512 (Electronic) Linking ISSN: 17576512 NLM ISO Abbreviation: Stem Cell Res Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central |
| مواضيع طبية MeSH: | Mesenchymal Stem Cells/*immunology , Minocycline/*pharmacology , NF-kappa B/*immunology , Staphylococcus aureus/*immunology, Adult ; Cells, Immobilized/immunology ; Female ; Humans ; Male ; Phosphorylation/drug effects ; Phosphorylation/immunology |
| مستخلص: | Background: Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties due to their anti-inflammatory, angiogenic, and even antibacterial properties. We have shown previously that minocycline enhances the wound healing phenotype of MSCs, and MSCs encapsulated in poly(ethylene glycol) and gelatin-based hydrogels with minocycline have antibacterial properties against Staphylococcus aureus (SA). Here, we investigated the signaling pathway that minocycline modulates in MSCs which results in their enhanced wound healing phenotype and determined whether preconditioning MSCs with minocycline has an effect on antimicrobial activity. We further investigated the in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels in inoculated full-thickness cutaneous wounds. Methods: Modulation of cell signaling pathways in MSCs with minocycline was analyzed via western blot, immunofluorescence, and ELISA. Antimicrobial efficacy of MSCs pretreated with minocycline was determined by direct and transwell coculture with SA. MSC viability after SA coculture was determined via a LIVE/DEAD® stain. Internalization of SA by MSCs pretreated with minocycline was determined via confocal imaging. All protein and cytokine analysis was done via ELISA. The in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels was determined in Sprague-Dawley rats inoculated with SA. Two-way ANOVA for multiple comparisons was used with Bonferroni test assessment and an unpaired two-tailed Student's t test was used to determine p values for all assays with multiple or two conditions, respectively. Results: Minocycline leads to the phosphorylation of transcriptional nuclear factor-κB (NFκB), but not c-Jun NH Conclusions: Minocycline modulates the NFκB pathway in MSCs that leads to an enhanced production of IL-6 and internalization of SA. This mechanism may have contributed to the in-vivo antibacterial efficacy of MSC and antibiotic-loaded hydrogels. |
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| معلومات مُعتمدة: | P30 CA014520 United States CA NCI NIH HHS; R21 HL115482 United States HL NHLBI NIH HHS; T32 GM008349 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: Animal model; Antimicrobial; Biomaterials; Hydrogel; Mesenchymal stem cells; Mesenchymal stromal cells; Minocycline; NFκB |
| المشرفين على المادة: | 0 (NF-kappa B) FYY3R43WGO (Minocycline) |
| تواريخ الأحداث: | Date Created: 20170723 Date Completed: 20180409 Latest Revision: 20181202 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5521110 |
| DOI: | 10.1186/s13287-017-0623-1 |
| PMID: | 28732530 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1757-6512 |
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| DOI: | 10.1186/s13287-017-0623-1 |