ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in Macrophages
A disintegrin and metalloprotease 10 (ADAM-10), a member of the ADAM protease family, has biological activities related to TNF-α activation, cell adhesion, and migration, among other functions. Macrophages are important immune cells that are involved in the inflammatory response of the body. ADAM-10...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/3012218 |
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| author | Yan Jiang Qiming Gong Jinmei Huang Yuanxun Gong Qiang Tang Dalong Wei Qianli Tang Jingjie Zhao Jian Song Lingzhang Meng |
| author_facet | Yan Jiang Qiming Gong Jinmei Huang Yuanxun Gong Qiang Tang Dalong Wei Qianli Tang Jingjie Zhao Jian Song Lingzhang Meng |
| author_sort | Yan Jiang |
| collection | DOAJ |
| description | A disintegrin and metalloprotease 10 (ADAM-10), a member of the ADAM protease family, has biological activities related to TNF-α activation, cell adhesion, and migration, among other functions. Macrophages are important immune cells that are involved in the inflammatory response of the body. ADAM-10 is involved in inflammatory responses, but the specific regulatory mechanisms are not fully understood. In this study, we investigated the regulatory mechanism of ADAM-10 in the lipopolysaccharide-promoted proliferation (LPS) of the macrophage inflammatory response. Differentially expressed or regulated proteins were identified in interfered ADAM-10 (sh ADAM-10) macrophages using tandem mass tag (TMT) proteomics. The changes and regulatory role of ADAM-10 during LPS-induced inflammatory response in normal, interfering, and overexpressing ADAM-10 (EX ADAM-10) cells were determined. Results indicated that ADAM-10 interference affected inflammation-related pathways and reduced matrix metalloproteinase 12 (MMP-12) protein levels, as identified by TMT proteomics. In normal cells, LPS decreased ADAM-10 gene expression, but promoted ADAM-10 secretion, MMP-12 and TNF-α gene expression, and MMP-12, iNOS, IL-10, and cyclinD1 protein expression. Additionally, ADAM-10 knockdown decreased macrophage viability in sh-ADAM-10 cells. Moreover, an MMP-12 inhibitor had no impact on the viability effect of LPS on cells or the expression of ADAM-10. iNOS expression decreased, whereas IL-10 expression increased after ADAM-10 depletion. ADAM-10 knockdown decreased MMP-12, iNOS, TNF-α, IL-1β, and FKN, while overexpression had an opposite effect. ADAM-10 overexpression further increased MMP-12, iNOS, and TNF-α gene expression in response to LPS. Cell viability was increased in EX ADAM-10 cells, and ADAM-10 secretion was further increased in the EX and LPS groups. Flow cytometry and immunofluorescence staining revealed that EX-ADAM 10 cells had increased iNOS expression, which acted as an IL-6 expression driver. In summary, we found that ADAM-10 is activated by LPS and positively participates in LPS-stimulated macrophage inflammatory responses by positively regulating MMP-12 during the inflammatory process. |
| format | Article |
| id | doaj-art-faba95cec79145ecbe4ba56a0a774c65 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-faba95cec79145ecbe4ba56a0a774c652025-02-03T05:49:19ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/3012218ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in MacrophagesYan Jiang0Qiming Gong1Jinmei Huang2Yuanxun Gong3Qiang Tang4Dalong Wei5Qianli Tang6Jingjie Zhao7Jian Song8Lingzhang Meng9Medical CollegeDepartment of NephrologyWest Guangxi Key Laboratory for Prevention and Treatment of High-Incidence DiseasesLife Science and Clinical Research CenterBurn Plastic & Trauma Surgery DepartmentBurn Plastic & Trauma Surgery DepartmentMedical CollegeLife Science and Clinical Research CenterCenter for Systemic Inflammation Research (CSIR)Center for Systemic Inflammation Research (CSIR)A disintegrin and metalloprotease 10 (ADAM-10), a member of the ADAM protease family, has biological activities related to TNF-α activation, cell adhesion, and migration, among other functions. Macrophages are important immune cells that are involved in the inflammatory response of the body. ADAM-10 is involved in inflammatory responses, but the specific regulatory mechanisms are not fully understood. In this study, we investigated the regulatory mechanism of ADAM-10 in the lipopolysaccharide-promoted proliferation (LPS) of the macrophage inflammatory response. Differentially expressed or regulated proteins were identified in interfered ADAM-10 (sh ADAM-10) macrophages using tandem mass tag (TMT) proteomics. The changes and regulatory role of ADAM-10 during LPS-induced inflammatory response in normal, interfering, and overexpressing ADAM-10 (EX ADAM-10) cells were determined. Results indicated that ADAM-10 interference affected inflammation-related pathways and reduced matrix metalloproteinase 12 (MMP-12) protein levels, as identified by TMT proteomics. In normal cells, LPS decreased ADAM-10 gene expression, but promoted ADAM-10 secretion, MMP-12 and TNF-α gene expression, and MMP-12, iNOS, IL-10, and cyclinD1 protein expression. Additionally, ADAM-10 knockdown decreased macrophage viability in sh-ADAM-10 cells. Moreover, an MMP-12 inhibitor had no impact on the viability effect of LPS on cells or the expression of ADAM-10. iNOS expression decreased, whereas IL-10 expression increased after ADAM-10 depletion. ADAM-10 knockdown decreased MMP-12, iNOS, TNF-α, IL-1β, and FKN, while overexpression had an opposite effect. ADAM-10 overexpression further increased MMP-12, iNOS, and TNF-α gene expression in response to LPS. Cell viability was increased in EX ADAM-10 cells, and ADAM-10 secretion was further increased in the EX and LPS groups. Flow cytometry and immunofluorescence staining revealed that EX-ADAM 10 cells had increased iNOS expression, which acted as an IL-6 expression driver. In summary, we found that ADAM-10 is activated by LPS and positively participates in LPS-stimulated macrophage inflammatory responses by positively regulating MMP-12 during the inflammatory process.http://dx.doi.org/10.1155/2022/3012218 |
| spellingShingle | Yan Jiang Qiming Gong Jinmei Huang Yuanxun Gong Qiang Tang Dalong Wei Qianli Tang Jingjie Zhao Jian Song Lingzhang Meng ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in Macrophages Journal of Immunology Research |
| title | ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in Macrophages |
| title_full | ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in Macrophages |
| title_fullStr | ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in Macrophages |
| title_full_unstemmed | ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in Macrophages |
| title_short | ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in Macrophages |
| title_sort | adam 10 regulates mmp 12 during lipopolysaccharide induced inflammatory response in macrophages |
| url | http://dx.doi.org/10.1155/2022/3012218 |
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