Sự ức chế của kinase protein p38 được kích hoạt bởi tác nhân gây ra tăng cường hoạt động kinase c-Jun N-terminal: Ý nghĩa trong sự biểu hiện của enzyme tổng hợp nitric oxide cảm ứng

BMC Pharmacology - 2006
Aleksi Lahti1, Outi Sareila1, Hannu Kankaanranta1, Eeva Moilanen1
1The Immunopharmacology Research Group, Medical School, University of Tampere and Tampere University Hospital, Tampere, Finland

Tóm tắt

Tóm tắtĐặt vấn đềOxide nitric (NO) là một tác nhân trung gian viêm, hoạt động như một chất độc tế bào và điều chỉnh phản ứng miễn dịch cũng như sự viêm nhiễm. Đường dẫn truyền tín hiệu kinase protein p38 (MAPK) được kích hoạt bởi căng thẳng hóa học và vật lý và điều tiết các phản ứng miễn dịch. Các nghiên cứu trước đây đã chỉ ra rằng đường dẫn MAPK p38 điều chỉnh sự sản xuất NO do kích thích viêm gây ra. Mục tiêu của nghiên cứu hiện tại là điều tra các cơ chế tham gia vào việc điều chỉnh tổng hợp NO có thể cảm ứng qua đường dẫn MAPK p38.Kết quảCác chất ức chế MAPK p38 là SB203580 và SB220025 đã kích thích sự biểu hiện của enzyme tổng hợp nitric oxide cảm ứng (iNOS) và sản xuất NO do lipopolysaccharide (LPS) gây ra ở các tế bào đại thực bào chuột J774.2. Sự gia tăng biểu hiện mRNA của iNOS có liên quan đến sự giảm phân hủy mRNA của iNOS. Sự điều trị bằng SB220025 cũng làm tăng hoạt động của kinase N-terminal c-Jun (JNK) do LPS gây ra. Đáng chú ý, ức chế JNK SP600125 đã đảo ngược hiệu ứng của SB220025 trên biểu hiện mRNA iNOS và sản xuất NO do LPS gây ra.Kết luậnCác kết quả cho thấy rằng sự ức chế p38 MAPK bởi SB220025 dẫn đến tăng cường hoạt động JNK, điều này dẫn đến ổn định hóa mRNA iNOS, làm gia tăng biểu hiện iNOS và sản xuất NO.

Từ khóa


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