Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells

Influenza A virus (IAV) poses global threats to human health. Acute respiratory distress syndrome and multi-organ dysfunction are major complications in patients with severe influenza infection. This may be explained by the recent studies which highlighted the role of the pulmonary endothelium as th...

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Main Authors:	Kwok, Hoi-Hin, Poon, Po-Ying, Fok, Siu-Ping, Ying-Kit Yue, Patrick, Mak, Nai-Ki, Chan, Michael Chi-Wai, Peiris, Joseph Sriyal Malik, Wong, Ricky Ngok-Shun
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702174/

id	pubmed-4702174
recordtype	oai_dc
spelling	pubmed-47021742016-01-14 Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells Kwok, Hoi-Hin Poon, Po-Ying Fok, Siu-Ping Ying-Kit Yue, Patrick Mak, Nai-Ki Chan, Michael Chi-Wai Peiris, Joseph Sriyal Malik Wong, Ricky Ngok-Shun Article Influenza A virus (IAV) poses global threats to human health. Acute respiratory distress syndrome and multi-organ dysfunction are major complications in patients with severe influenza infection. This may be explained by the recent studies which highlighted the role of the pulmonary endothelium as the center of innate immune cells recruitment and excessive pro-inflammatory cytokines production. In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3′-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3′-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs). Infection of H9N2 on HPMECs induced a high level of chemokines and cytokines production including IP-10, RANTES, IL-6, IFN-β and IFN-γ1. Post-treatment of E804 or E231 could significantly suppress the production of these cytokines. H9N2 infection rapidly triggered the activation of innate immunity through phosphorylation of signaling molecules including mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT) proteins. Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways. These results underscore the immunomodulatory effects of indirubin derivatives on pulmonary endothelium and its therapeutic potential on IAV-infection. Nature Publishing Group 2016-01-06 /pmc/articles/PMC4702174/ /pubmed/26732368 http://dx.doi.org/10.1038/srep18941 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kwok, Hoi-Hin Poon, Po-Ying Fok, Siu-Ping Ying-Kit Yue, Patrick Mak, Nai-Ki Chan, Michael Chi-Wai Peiris, Joseph Sriyal Malik Wong, Ricky Ngok-Shun
spellingShingle	Kwok, Hoi-Hin Poon, Po-Ying Fok, Siu-Ping Ying-Kit Yue, Patrick Mak, Nai-Ki Chan, Michael Chi-Wai Peiris, Joseph Sriyal Malik Wong, Ricky Ngok-Shun Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells
author_facet	Kwok, Hoi-Hin Poon, Po-Ying Fok, Siu-Ping Ying-Kit Yue, Patrick Mak, Nai-Ki Chan, Michael Chi-Wai Peiris, Joseph Sriyal Malik Wong, Ricky Ngok-Shun
author_sort	Kwok, Hoi-Hin
title	Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells
title_short	Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells
title_full	Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells
title_fullStr	Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells
title_full_unstemmed	Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells
title_sort	anti-inflammatory effects of indirubin derivatives on influenza a virus-infected human pulmonary microvascular endothelial cells
description	Influenza A virus (IAV) poses global threats to human health. Acute respiratory distress syndrome and multi-organ dysfunction are major complications in patients with severe influenza infection. This may be explained by the recent studies which highlighted the role of the pulmonary endothelium as the center of innate immune cells recruitment and excessive pro-inflammatory cytokines production. In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3′-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3′-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs). Infection of H9N2 on HPMECs induced a high level of chemokines and cytokines production including IP-10, RANTES, IL-6, IFN-β and IFN-γ1. Post-treatment of E804 or E231 could significantly suppress the production of these cytokines. H9N2 infection rapidly triggered the activation of innate immunity through phosphorylation of signaling molecules including mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT) proteins. Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways. These results underscore the immunomodulatory effects of indirubin derivatives on pulmonary endothelium and its therapeutic potential on IAV-infection.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702174/
_version_	1613520340376354816

Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells

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