Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells
Epithelial cells in periodontitis patients increasingly express chemokines, suggesting their active involvement in the inflammatory process. Enamel matrix derivative (EMD) is an extract of porcine fetal tooth germs clinically applied to support the regrowth of periodontal tissues. Periodontal regene...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/13991 |
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| author | Layla Panahipour Sara Botta Azarakhsh Oladzad Abbasabadi Zohreh Afradi Reinhard Gruber |
| author_facet | Layla Panahipour Sara Botta Azarakhsh Oladzad Abbasabadi Zohreh Afradi Reinhard Gruber |
| author_sort | Layla Panahipour |
| collection | DOAJ |
| description | Epithelial cells in periodontitis patients increasingly express chemokines, suggesting their active involvement in the inflammatory process. Enamel matrix derivative (EMD) is an extract of porcine fetal tooth germs clinically applied to support the regrowth of periodontal tissues. Periodontal regeneration might benefit from the potential anti-inflammatory activity of EMD for epithelial cells. Our aim was, therefore, to set up a bioassay where chemokine expression is initiated in the HSC2 oral squamous carcinoma cell line and then test EMD for its capacity to lower the inflammatory response. To establish the bioassay, HSC2 cells being exposed to TNFα and LPS from <i>E. coli</i> (<i>Escherichia coli</i>) or <i>P. gingivalis</i> (<i>Porphyromonas gingivalis</i>) were subjected to RNAseq. Here, TNFα but not LPS caused a robust increase of chemokines, including CXCL1, CXCL2, CXCL8, CCL5, and CCL20 in HSC2 cells. Polymerase chain reaction confirmed the increased expression of the respective chemokines in cells exposed to TNFα and IL-1β. Under these conditions, EMD reduced the expression of all chemokines at the transcriptional level and CXCL8 by immunoassay. The TGF-β receptor type I kinase-inhibitor SB431542 reversed the anti-inflammatory activity. Moreover, EMD-activated TGF-β-canonical signaling was visualized by phosphorylation of smad3 and nuclear translocation of smad2/3 in HSC2 cells and blocked by SB431542. This observation was confirmed with primary oral epithelial cells where EMD significantly lowered the SB431542-dependent expression of CXCL8. In summary, our findings suggest that TGF-β signaling mediates the effects of EMD to lower the forced expression of chemokines in oral epithelial cells. |
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| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:40:05Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2ee704dbb1c24199853cf000373a3f3f2023-11-19T11:06:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181399110.3390/ijms241813991Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial CellsLayla Panahipour0Sara Botta1Azarakhsh Oladzad Abbasabadi2Zohreh Afradi3Reinhard Gruber4Department of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, AustriaDepartment of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, AustriaDepartment of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, AustriaDepartment of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, AustriaDepartment of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, AustriaEpithelial cells in periodontitis patients increasingly express chemokines, suggesting their active involvement in the inflammatory process. Enamel matrix derivative (EMD) is an extract of porcine fetal tooth germs clinically applied to support the regrowth of periodontal tissues. Periodontal regeneration might benefit from the potential anti-inflammatory activity of EMD for epithelial cells. Our aim was, therefore, to set up a bioassay where chemokine expression is initiated in the HSC2 oral squamous carcinoma cell line and then test EMD for its capacity to lower the inflammatory response. To establish the bioassay, HSC2 cells being exposed to TNFα and LPS from <i>E. coli</i> (<i>Escherichia coli</i>) or <i>P. gingivalis</i> (<i>Porphyromonas gingivalis</i>) were subjected to RNAseq. Here, TNFα but not LPS caused a robust increase of chemokines, including CXCL1, CXCL2, CXCL8, CCL5, and CCL20 in HSC2 cells. Polymerase chain reaction confirmed the increased expression of the respective chemokines in cells exposed to TNFα and IL-1β. Under these conditions, EMD reduced the expression of all chemokines at the transcriptional level and CXCL8 by immunoassay. The TGF-β receptor type I kinase-inhibitor SB431542 reversed the anti-inflammatory activity. Moreover, EMD-activated TGF-β-canonical signaling was visualized by phosphorylation of smad3 and nuclear translocation of smad2/3 in HSC2 cells and blocked by SB431542. This observation was confirmed with primary oral epithelial cells where EMD significantly lowered the SB431542-dependent expression of CXCL8. In summary, our findings suggest that TGF-β signaling mediates the effects of EMD to lower the forced expression of chemokines in oral epithelial cells.https://www.mdpi.com/1422-0067/24/18/13991enamel matrix derivativeoral epithelial cellschemokinesbioassayinflammationperiodontitis |
| spellingShingle | Layla Panahipour Sara Botta Azarakhsh Oladzad Abbasabadi Zohreh Afradi Reinhard Gruber Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells International Journal of Molecular Sciences enamel matrix derivative oral epithelial cells chemokines bioassay inflammation periodontitis |
| title | Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells |
| title_full | Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells |
| title_fullStr | Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells |
| title_full_unstemmed | Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells |
| title_short | Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells |
| title_sort | enamel matrix derivative suppresses chemokine expression in oral epithelial cells |
| topic | enamel matrix derivative oral epithelial cells chemokines bioassay inflammation periodontitis |
| url | https://www.mdpi.com/1422-0067/24/18/13991 |
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