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25.05.2019 | ORIGINAL ARTICLE | Ausgabe 5/2019

Inflammation 5/2019

Novel Piperazino-Enaminones Decrease Pro-inflammatory Cytokines Following Hemarthrosis in a Hemophilia Mouse Model

Zeitschrift:
Inflammation > Ausgabe 5/2019
Autoren:
Chen Zhong, Doreen Szollosi, Junjiang Sun, Baolai Hua, Ola Ghoneim, Ashley Bill, Yingping Zhuang, Ivan Edafiogho
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10753-019-01032-y) contains supplementary material, which is available to authorized users.
Chen Zhong, Doreen Szollosi, and Junjiang Sun contributed equally to this work.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Hemarthrosis is the primary cause of hemophiliac arthropathy (HA). Pro-inflammatory cytokines are thought to play an important role in the pathogenesis of HA, and thus, anti-cytokine approaches may be used as an adjuvant therapy. A novel series of enaminone compounds (JODI), that contain the N-aryl piperazino motif, have been shown in vitro to reduce pro-inflammatory cytokines and thus may be efficacious in vivo. In this report, we will assess whether JODI can suppress multiple cytokines which might be potentially responsible for joint inflammation in a mouse model of hemarthrosis. The results showed that JODI significantly improved the survival after LPS treatment, and most pro-inflammatory cytokines/chemokines were decreased significantly after JODI administration. In the hemophilia mouse model, hemarthrosis resulted in local cytokine/chemokine changes, represented by elevated pro-inflammatory (IL-6, MCP-1, MIP-1α, MIP-1β) and pro-angiogenic (VEGF and IL-33) cytokines, and decreased anti-pro-inflammatory cytokines IL-4 and IL-10. The changes were reversed by administration of JODI, which can be used as a novel approach to manage hemophilia arthropathy.

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