IL-1beta receptor blockade protects islets against pro-inflammatory cytokine induced necrosis and apoptosis.
IL-1beta receptor blockade protects islets against pro-inflammatory cytokine induced necrosis and apoptosis.
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DOI：
10.1002/jcp.21770
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发表时间：
2009-08
影响因子：
5.6
通讯作者：
Fernandez, Luis A.
中科院分区：
文献类型：
--
作者：
Schwarznau, Alice;Hanson, Matthew S.;Sperger, Jamie M.;Schram, Brian R.;Danobeitia, Juan S.;Greenwood, Krista K.;Vijayan, Ashwanth;Fernandez, Luis A.
Pro-inflammatory cytokines (PIC) impair islet viability and function by activating inflammatory pathways that induce both necrosis and apoptosis. The aim of this study was to utilize an in vitro rat islet model to evaluate the efficacy of a clinically approved IL-1 receptor antagonist (Anakinra) in blocking PIC induced islet impairment. Isolated rat islets were cultured for 48h ± PIC (IL-1β, IFNγ, and TNFα and ±IL-1ra then assayed for cellular integrity by flow cytometry, MAPK phosphorylation by proteome array, and gene expression by RT-PCR. Nitric oxide (NO) release into the culture media was measured by Griess reaction. Islet functional potency was tested by glucose stimulated insulin secretion (GSIS) and by transplantation into streptozotocin-induced diabetic NOD.scid mice. Rat islets cultured with PIC upregulated genes for NOS2a, COX2, IL6, IL1b, TNFa, and HMOX1. IL-1ra prevented the PIC induced upregulation of all of these genes except for TNFa. Inhibition of PIC induced iNOS by NG-monomethyl-L-arginine (NMMA) only blocked the increased expression of HMOX1. IL-1ra completely abrogated the effects of PIC with respect to NO production, necrosis, apoptosis, mitochondrial dysfunction, GSIS, and in vivo potency. IL-1ra was not effective at preventing the induction of necrosis or apoptosis by exogenous NO. These data demonstrate that Anakinra is an effective agent to inhibit the activation of IL-1β dependent inflammatory pathways in cultured rat islets and support the extension of its application to human islets in vitro and potentially as a post transplant therapy.
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影响因子：
8.2
作者：
Kato, Y;Miura, Y;Oiso, Y
通讯作者：
Oiso, Y
影响因子：
5.6
作者：
Papaccio, G;Graziano, A;Nicoletti, F
通讯作者：
Nicoletti, F
DOI：
10.1073/pnas.90.5.1731
发表时间：
1993-03-01
影响因子：
11.1
作者：
CORBETT, JA;SWEETLAND, MA;MCDANIEL, ML
通讯作者：
MCDANIEL, ML
影响因子：
7.7
作者：
Kaneto, H;Kajimoto, Y;Hori, M
通讯作者：
Hori, M
影响因子：
15.3
作者：
KAUFMAN, DB;PLATT, JL;SUTHERLAND, DER
通讯作者：
SUTHERLAND, DER