Journal info
|
||
Select Journal
Journals
Bratislava Medical Journal Endocrine Regulations General Physiology and Biophysics Neoplasma Acta Virologica Current articles 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 Studia Psychologica Cardiology Letters Psychológia a patopsych. dieťaťa Kovove Materialy-Metallic Materials Slovenská hudbaWebshop Cart
Your Cart is currently empty.
Info: Your browser does not accept cookies. To put products into your cart and purchase them you need to enable cookies.
Acta Virologica Vol.55, No.3, p.243-253, 2011 |
||
Title: Blockade of Lyn kinase upregulates both canonical and non-canonical TLR-3 pathways in THP-1 monocytes exposed to human cytomegalovirus | ||
Author: K. H. YEW, C. J. HARRISON | ||
Abstract: Regulation of monocyte response to human cytomegalovirus (HCMV) occurs via activation of receptors that elicit innate antiviral effects and later T-cell responses. Our previous data (Yew et al.., 2010) demonstrated that human monocyte scavenger receptor A type 1 (SR-A1) are required for sensing of HCMV by endosomal toll-like receptors (TLRs)-3 and -9, which in turn induce critical pro-inflammatory cytokines. However, it remains unclear which subcellular molecules associated with SR-A1 lead to downstream activation of TLR-3 and/or TLR-9 signaling pathways. Herein we report that Lyn kinase, associated physically and functionally with SR-A for low density lipoprotein (LDL) recognition, acts as a key SR-A1-induced kinase that plays a critical role in TLR-3/9 signal transduction upon HCMV exposure to THP-1 monocytes. We found that disruption of the SR-A1 signal transduction through molecular inhibition by Lyn kinase oligonucleotides not only blocks the activation of downstream TLR-9 pathway but also alters the downstream TLR-3 pathway. In particular, Lyn kinase oligonucleotides resulted in decreased expression of TLR-9-induced tumor necrosis factor alpha (TNF-α) but strongly upregulated canonical TLR-3-induced interferon beta (IFN-β) and non-canonical TLR-3-induced NF-κB-dependent p35 (35kDa) subunit of interleukin 12 (IL-12p35) gene transcription. Thus, the observed shift away from TNF-α to robust IFN-β and IL-12p35 induction may offer opportunities for therapeutic interventions. |
||
Keywords: HCMV; THP-1 monocytes; TLR-3/-9; Lyn kinase; TNF-α; IFN-β; IL-12p35 | ||
Year: 2011, Volume: 55, Issue: 3 | Page From: 243, Page To: 253 | |
doi:10.4149/av_2011_03_243 |
||
|
download file |
|