Roles of Bcl-2 and caspase-9 and -3 in CD30-induced human eosinophil apoptosis

Autor: Hye Jin Lee, Eun-Kyoung Lee, Young Eun Seo, Youn Ho Shin, Hwan Soo Kim, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Man Yong Han, Chang-Keun Kim, Kyu-Earn Kim, Young Yull Koh, Jin Tack Kim
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Journal of Microbiology, Immunology and Infection, Vol 50, Iss 2, Pp 145-152 (2017)
Druh dokumentu: article
ISSN: 1684-1182
DOI: 10.1016/j.jmii.2015.05.017
Popis: Background/purpose: Activation of cell surface CD30 by immobilized anti-CD30 monoclonal antibodies (mAb) induces strong apoptosis in human eosinophils. This anti-CD30 mAb-induced eosinophil apoptosis is inhibited by the addition of inhibitors of p38, ERK1/2 mitogen-activated protein kinases, and phosphatidylinositol 3-kinase. However, there is little data investigating the role of Bcl-2 and caspases in eosinophil apoptosis induced by anti-CD30 mAb. We sought to determine whether anti-CD30 mAb induces human eosinophil apoptosis via Bcl-2 and caspase pathways. Methods: Peripheral blood was drawn from 37 healthy volunteers. The CD30 expression on eosinophils was measured at various time points. Eosinophils were then cultured in plates precoated with anti-CD30 mAb (clone Ber-H8), isotype control immunoglobulin G1, interleukin (IL)-5, or dexamethasone. Western blot analysis was performed to determine the expression of Bcl-2, procaspase-8, -9, and -3, and caspase-8, -9, and -3 after cross-linking of CD30. Human eosinophils were also cultured in plates precoated with anti-CD30 mAb (clone Ber-H8) in the presence or absence of caspase-9 or -3 inhibitors. Eosinophil apoptosis was assessed using flow cytometry. Results: The addition of anti-CD30 mAb significantly increased eosinophil apoptosis compared with controls. In western blot analysis, the addition of anti-CD30 mAb significantly decreased the expression of Bcl-2 and procaspase-9 and -3 and increased the expression of caspase-9 and -3. The addition of caspase-9 or -3 inhibitors decreased anti-CD30 mAb-induced human eosinophil apoptosis. Procaspase-8 or caspase-8 expression was not changed in response to various stimuli. Conclusion: Anti-CD30 mAb-induced human eosinophil apoptosis is likely to be mediated through Bcl-2 and caspase-9 and -3.
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