BMP-6 ức chế sự phát triển của các tế bào B trưởng thành ở người; kích thích phosphorylation Smad và tăng cường biểu hiện Id1

BMC Immunology - Tập 6 - Trang 1-13 - 2005
Christian Kersten1, Einar A Sivertsen1, Marit E Hystad1, Lise Forfang1, Erlend B Smeland1,2, June H Myklebust1
1Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
2Faculty Division, The Norwegian Radium Hospital, University of Oslo, Norway

Tóm tắt

Protein tạo hình xương (BMP) thuộc siêu họ TGF-β và là các protein được tiết ra với nhiều vai trò khác nhau ở nhiều loại tế bào. Một vai trò tiềm năng của BMP-6 trong hệ miễn dịch đã được ngụ ý qua nhiều nghiên cứu về các bệnh ác tính và viêm khớp. Trong nghiên cứu này, chúng tôi đã khám phá vai trò của BMP-6 trong các tế bào B ngoại vi máu ở người bình thường. Các tế bào B được phát hiện có biểu hiện thụ thể loại I và loại II của BMP, và BMP-6 nhanh chóng kích thích phosphoryl hóa Smad1/5/8. Hơn nữa, việc phosphoryl hóa Smad dẫn đến việc tăng cường mRNA Id1 và protein Id1, trong khi biểu hiện Id2 và Id3 không bị ảnh hưởng. Thêm vào đó, chúng tôi phát hiện rằng BMP-6 có tác động ức chế sinh sản đối với cả tế bào B chưa trưởng thành (CD19+CD27-) và tế bào B ghi nhớ (CD19+CD27+) khi được kích thích bằng anti-IgM hoặc sự kết hợp của anti-IgM và CD40L. Ngoài ra, BMP-6 đã gây ra cái chết tế bào trong các tế bào B ghi nhớ đã được kích hoạt. Quan trọng hơn, tác động ức chế sinh sản của BMP-6 trong các tế bào B đã bị trung hòa hoàn toàn bởi đối kháng tự nhiên, noggin. Thêm vào đó, các tế bào B được chứng minh là tăng cường mRNA BMP-6 khi được kích thích bằng anti-IgM. Ở các tế bào B trưởng thành của người, BMP-6 đã ức chế sự phát triển tế bào và nhanh chóng kích thích phosphoryl hóa Smad1/5/8, tiếp theo là tăng cường biểu hiện Id1.

Từ khóa

#BMP-6 #tế bào B trưởng thành #phosphoryl hóa Smad #Id1 #hệ miễn dịch

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