Interleukin-37 reduces lipopolysaccharide induced matrix metalloproteinase-9 in gingival epithelial cells
Abstract Background In periodontal diseases, the recognition of pathogen-associated molecular patterns (PAMPs) triggers signaling cascades that lead to the release of matrix metalloproteinases (MMPs). Interleukin-37 (IL-37) is recognized as a key suppressor of the immune response. This study aimed t...
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2025-04-01
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| Series: | BMC Oral Health |
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| Online Access: | https://doi.org/10.1186/s12903-025-06016-z |
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| author | Arzu Beklen Muhammet Burak Yavuz Deniz Uckan |
| author_facet | Arzu Beklen Muhammet Burak Yavuz Deniz Uckan |
| author_sort | Arzu Beklen |
| collection | DOAJ |
| description | Abstract Background In periodontal diseases, the recognition of pathogen-associated molecular patterns (PAMPs) triggers signaling cascades that lead to the release of matrix metalloproteinases (MMPs). Interleukin-37 (IL-37) is recognized as a key suppressor of the immune response. This study aimed to detect the expression and distribution of IL-37 in gingival tissues and analyze its suppressor role in MMP-9 in response to lipopolysaccharide (LPS)-stimulated gingival epithelial cells. Methods Immunohistochemistry localized IL-37 in gingival tissues from periodontitis patients and healthy controls (N = 10). The induction of IL-37 expression by LPS was analyzed using the conditioned medium of gingival epithelial cells through enzyme-linked immunosorbent assay (ELISA). To determine the relevant MMP-9 levels in epithelial cells following exposure to LPS alone or in combination with IL-37, both quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) were performed. Results Cultured epithelial cells secreted significantly higher levels of IL-37 when stimulated with LPS compared to unstimulated controls. Both ELISA and qPCR showed that LPS stimulation significantly increased MMP-9 levels. However, co-culture with IL-37 markedly reduced LPS-induced MMP-9 expression at both the protein and mRNA levels. Furthermore, immunohistochemistry revealed increased IL-37 expression in periodontitis tissues, both in epithelial cells and connective tissue. Conclusions Gingival epithelial cells may contribute to tissue responses in periodontitis through the secretion of MMP-9 in response to PAMPs. Furthermore, IL-37 appears to have a potential role in modulating and reducing this response, as observed in the decreased MMP-9 expression following IL-37 co-stimulation. |
| format | Article |
| id | doaj-art-620da54bb5ca4ed7bd3c38fc99def183 |
| institution | OA Journals |
| issn | 1472-6831 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Oral Health |
| spelling | doaj-art-620da54bb5ca4ed7bd3c38fc99def1832025-08-20T02:19:57ZengBMCBMC Oral Health1472-68312025-04-012511910.1186/s12903-025-06016-zInterleukin-37 reduces lipopolysaccharide induced matrix metalloproteinase-9 in gingival epithelial cellsArzu Beklen0Muhammet Burak Yavuz1Deniz Uckan2Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of HelsinkiDepartment of Periodontology, Faculty of Dentistry, Eskisehir Osmangazi UniversityBogazici University, Medico-Social Dental ClinicAbstract Background In periodontal diseases, the recognition of pathogen-associated molecular patterns (PAMPs) triggers signaling cascades that lead to the release of matrix metalloproteinases (MMPs). Interleukin-37 (IL-37) is recognized as a key suppressor of the immune response. This study aimed to detect the expression and distribution of IL-37 in gingival tissues and analyze its suppressor role in MMP-9 in response to lipopolysaccharide (LPS)-stimulated gingival epithelial cells. Methods Immunohistochemistry localized IL-37 in gingival tissues from periodontitis patients and healthy controls (N = 10). The induction of IL-37 expression by LPS was analyzed using the conditioned medium of gingival epithelial cells through enzyme-linked immunosorbent assay (ELISA). To determine the relevant MMP-9 levels in epithelial cells following exposure to LPS alone or in combination with IL-37, both quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) were performed. Results Cultured epithelial cells secreted significantly higher levels of IL-37 when stimulated with LPS compared to unstimulated controls. Both ELISA and qPCR showed that LPS stimulation significantly increased MMP-9 levels. However, co-culture with IL-37 markedly reduced LPS-induced MMP-9 expression at both the protein and mRNA levels. Furthermore, immunohistochemistry revealed increased IL-37 expression in periodontitis tissues, both in epithelial cells and connective tissue. Conclusions Gingival epithelial cells may contribute to tissue responses in periodontitis through the secretion of MMP-9 in response to PAMPs. Furthermore, IL-37 appears to have a potential role in modulating and reducing this response, as observed in the decreased MMP-9 expression following IL-37 co-stimulation.https://doi.org/10.1186/s12903-025-06016-zEpithelial cellsIL-37LPSMMP-9Periodontitis |
| spellingShingle | Arzu Beklen Muhammet Burak Yavuz Deniz Uckan Interleukin-37 reduces lipopolysaccharide induced matrix metalloproteinase-9 in gingival epithelial cells BMC Oral Health Epithelial cells IL-37 LPS MMP-9 Periodontitis |
| title | Interleukin-37 reduces lipopolysaccharide induced matrix metalloproteinase-9 in gingival epithelial cells |
| title_full | Interleukin-37 reduces lipopolysaccharide induced matrix metalloproteinase-9 in gingival epithelial cells |
| title_fullStr | Interleukin-37 reduces lipopolysaccharide induced matrix metalloproteinase-9 in gingival epithelial cells |
| title_full_unstemmed | Interleukin-37 reduces lipopolysaccharide induced matrix metalloproteinase-9 in gingival epithelial cells |
| title_short | Interleukin-37 reduces lipopolysaccharide induced matrix metalloproteinase-9 in gingival epithelial cells |
| title_sort | interleukin 37 reduces lipopolysaccharide induced matrix metalloproteinase 9 in gingival epithelial cells |
| topic | Epithelial cells IL-37 LPS MMP-9 Periodontitis |
| url | https://doi.org/10.1186/s12903-025-06016-z |
| work_keys_str_mv | AT arzubeklen interleukin37reduceslipopolysaccharideinducedmatrixmetalloproteinase9ingingivalepithelialcells AT muhammetburakyavuz interleukin37reduceslipopolysaccharideinducedmatrixmetalloproteinase9ingingivalepithelialcells AT denizuckan interleukin37reduceslipopolysaccharideinducedmatrixmetalloproteinase9ingingivalepithelialcells |