Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis
Background Sulfation of heparan sulfate proteoglycans (HSPGs) is critical for the binding and signaling of ligands that mediate inflammation. Extracellular 6-O-endosulfatases regulate posttranslational sulfation levels and patterns of HSPGs. In this study, extracellular 6-O-endosulfatases, sulfatase...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Yeungnam University College of Medicine
2021-10-01
|
| Series: | Yeungnam University Journal of Medicine |
| Subjects: | |
| Online Access: | http://www.e-jyms.org/upload/pdf/yujm-2021-01025.pdf |
| _version_ | 1798035618850144256 |
|---|---|
| author | Hyun-Je Kim Hee-Sun Kim Young-Hoon Hong |
| author_facet | Hyun-Je Kim Hee-Sun Kim Young-Hoon Hong |
| author_sort | Hyun-Je Kim |
| collection | DOAJ |
| description | Background Sulfation of heparan sulfate proteoglycans (HSPGs) is critical for the binding and signaling of ligands that mediate inflammation. Extracellular 6-O-endosulfatases regulate posttranslational sulfation levels and patterns of HSPGs. In this study, extracellular 6-O-endosulfatases, sulfatase (Sulf)-1 and Sulf-2, were evaluated for their expression and function in inflammatory cells and tissues. Methods Harvested human peripheral blood mononuclear cells were treated with phytohemagglutinin and lipopolysaccharide, and murine peritoneal macrophages were stimulated with interleukin (IL)-1β for the evaluation of Sulf-1 and Sulf-2 expression. Sulf expression in inflammatory cells was examined in the human rheumatoid arthritis (RA) synovium by immunofluorescence staining. The antigen presentation and phagocytic activities of macrophages were compared according to the expression state of Sulfs. Sulfs-knockdown macrophages and Sulfs-overexpressing macrophages were generated using small interfering RNAs and pcDNA3.1 plasmids for Sulf-1 and Sulf-2, respectively. Results Lymphocytes and monocytes showed weak Sulf expression, which remained unaffected by IL-1β. However, peritoneal macrophages showed increased expression of Sulfs upon stimulation with IL-1β. In human RA synovium, two-colored double immunofluorescent staining of Sulfs and CD68 revealed active upregulation of Sulfs in macrophages of inflamed tissues, but not in lymphocytes of lymphoid follicles. Macrophages are professional antigen-presenting cells. The antigen presentation and phagocytic activities of macrophages were dependent on the level of Sulf expression, suppressed in Sulfs-knockdown macrophages, and enhanced in Sulfs-overexpressing macrophages. Conclusion The results demonstrate that upregulation of Sulfs in macrophages occurs in response to inflammation, and Sulfs actively regulate the antigen presentation and phagocytic activities of macrophages as novel immune regulators. |
| first_indexed | 2024-04-11T21:00:45Z |
| format | Article |
| id | doaj.art-13d4ef409f3b4cb1b65c3dadbc7f252a |
| institution | Directory Open Access Journal |
| issn | 2384-0293 |
| language | English |
| last_indexed | 2024-04-11T21:00:45Z |
| publishDate | 2021-10-01 |
| publisher | Yeungnam University College of Medicine |
| record_format | Article |
| series | Yeungnam University Journal of Medicine |
| spelling | doaj.art-13d4ef409f3b4cb1b65c3dadbc7f252a2022-12-22T04:03:30ZengYeungnam University College of MedicineYeungnam University Journal of Medicine2384-02932021-10-0138432633610.12701/yujm.2021.010252651Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosisHyun-Je Kim0Hee-Sun Kim1Young-Hoon Hong2 Division of Rheumatology, Department of Internal Medicine, CHA University, CHA Gumi Medical Center, Gumi, Korea Department of Microbiology, Yeungnam University College of Medicine, Daegu, Korea Division of Rheumatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, KoreaBackground Sulfation of heparan sulfate proteoglycans (HSPGs) is critical for the binding and signaling of ligands that mediate inflammation. Extracellular 6-O-endosulfatases regulate posttranslational sulfation levels and patterns of HSPGs. In this study, extracellular 6-O-endosulfatases, sulfatase (Sulf)-1 and Sulf-2, were evaluated for their expression and function in inflammatory cells and tissues. Methods Harvested human peripheral blood mononuclear cells were treated with phytohemagglutinin and lipopolysaccharide, and murine peritoneal macrophages were stimulated with interleukin (IL)-1β for the evaluation of Sulf-1 and Sulf-2 expression. Sulf expression in inflammatory cells was examined in the human rheumatoid arthritis (RA) synovium by immunofluorescence staining. The antigen presentation and phagocytic activities of macrophages were compared according to the expression state of Sulfs. Sulfs-knockdown macrophages and Sulfs-overexpressing macrophages were generated using small interfering RNAs and pcDNA3.1 plasmids for Sulf-1 and Sulf-2, respectively. Results Lymphocytes and monocytes showed weak Sulf expression, which remained unaffected by IL-1β. However, peritoneal macrophages showed increased expression of Sulfs upon stimulation with IL-1β. In human RA synovium, two-colored double immunofluorescent staining of Sulfs and CD68 revealed active upregulation of Sulfs in macrophages of inflamed tissues, but not in lymphocytes of lymphoid follicles. Macrophages are professional antigen-presenting cells. The antigen presentation and phagocytic activities of macrophages were dependent on the level of Sulf expression, suppressed in Sulfs-knockdown macrophages, and enhanced in Sulfs-overexpressing macrophages. Conclusion The results demonstrate that upregulation of Sulfs in macrophages occurs in response to inflammation, and Sulfs actively regulate the antigen presentation and phagocytic activities of macrophages as novel immune regulators.http://www.e-jyms.org/upload/pdf/yujm-2021-01025.pdfantigen presentationmacrophagessulfatase 1sulfatase 2 |
| spellingShingle | Hyun-Je Kim Hee-Sun Kim Young-Hoon Hong Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis Yeungnam University Journal of Medicine antigen presentation macrophages sulfatase 1 sulfatase 2 |
| title | Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis |
| title_full | Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis |
| title_fullStr | Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis |
| title_full_unstemmed | Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis |
| title_short | Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis |
| title_sort | sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis |
| topic | antigen presentation macrophages sulfatase 1 sulfatase 2 |
| url | http://www.e-jyms.org/upload/pdf/yujm-2021-01025.pdf |
| work_keys_str_mv | AT hyunjekim sulfatase1andsulfatase2asnovelregulatorsofmacrophageantigenpresentationandphagocytosis AT heesunkim sulfatase1andsulfatase2asnovelregulatorsofmacrophageantigenpresentationandphagocytosis AT younghoonhong sulfatase1andsulfatase2asnovelregulatorsofmacrophageantigenpresentationandphagocytosis |