Vai trò của protein thoái hóa vú 39 (BRP-39)/Chitinase 3-like-1 trong phản ứng mô và quá trình apoptosis gây ra bởi Th2 và IL-13

Journal of Experimental Medicine - Tập 206 Số 5 - Trang 1149-1166 - 2009
Chun Geun Lee1,2,3, Dominik Hartl1,2,3, Gap Ryol Lee1,2,3, Barbara Koller1,2,3, Hiroshi Matsuura1,2,3, Carla A. Da Silva1,2,3, Myung Hyun Sohn1,2,3, Lauren Cohn1,2,3, Robert Homer1,2,3, Alexander Kozhich4, Alison A. Humbles4, Jennifer Kearley4, Anthony J. Coyle4, Geoffrey Chupp1,2,3, Jennifer L. Reed4, Richard A. Flavell4, Jack A. Elias1,2,3
1Department of Pathology, Yale University School of Medicine, New Haven, CT 06520 1 , 2 , and 3
2Section of Immunobiology 1 , 2 , and 3
3Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Section of Immunobiology, and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520
4MedImmune, Inc., Gaithersburg, MD 20878 4

Tóm tắt

Protein thoái hóa vú chuột 39 (BRP-39; Chi3l1) và protein đồng dạng ở người YKL-40 là các protein giống chitinase nhưng thiếu hoạt tính chitinase. Mặc dù YKL-40 được biểu hiện với số lượng lớn và có sự tương quan với hoạt động bệnh ở hen suyễn và nhiều rối loạn khác, tính chất sinh học của BRP-39/YKL-40 chỉ mới được xác định một cách sơ sài. Chúng tôi mô tả việc tạo ra và đặc tính của chuột BRP-39−/−, chuột chuyển gen YKL-40 và chuột thiếu BRP-39 nhưng chỉ sản xuất YKL-40 trong biểu mô phổi. Các nghiên cứu trên các chuột này cho thấy các động vật BRP-39−/− có đáp ứng Th2 do kháng nguyên gây ra suy giảm rõ rệt và YKL-40 biểu mô cứu vãn các đáp ứng Th2 ở các động vật này. Khả năng của interleukin-13 gây viêm và xơ hóa mô cũng bị suy giảm rõ rệt khi thiếu BRP-39. Các nghiên cứu cơ chế cho thấy BRP-39 và YKL-40 đóng vai trò thiết yếu trong cảm ứng kháng nguyên và kích thích miễn dịch globulin E, kích thích sự tích lũy và hoạt hóa tế bào đuôi gai, cũng như kích hoạt đại thực bào thay thế. Các protein này cũng ức chế apoptosis/chết tế bào của các tế bào viêm trong khi ức chế biểu hiện Fas, kích hoạt protein kinase B/AKT và cảm ứng Faim 3. Các nghiên cứu này thiết lập vai trò điều tiết mới cho BRP-39/YKL-40 trong giai đoạn khởi đầu và hiệu ứng của Th2 viêm và tái cấu trúc, và cho thấy các protein này là các mục tiêu điều trị trong các rối loạn do Th2 và đại thực bào gây ra.

Từ khóa

#BRP-39 #YKL-40 #chitinase 3-like-1 #Th2 #IL-13 #apoptosis #protein kinase B/AKT #cảm ứng Faim 3 #điều tiết viêm #đại thực bào.

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