Activation of the interferon (IFN) pathway in response to infection with pathogens results in the induction of IFN-stimulated genes (ISGs) including proinflammatory cytokines, which mount the proper antiviral immune response. However, aberrant expression of these genes is pathogenic to the host. In addition to IFN-induced transcription factors non-IFN-regulated factors contribute to the transcriptional control of ISGs. Here, we show by genome wide expression analysis, siRNA-mediated suppression and Doxycycline-induced overexpression that the cellular transcription factor ZNF395 activates a subset of ISGs including the chemokines CXCL10 and CXCL11 in keratinocytes. We found that ZNF395 acts independently of IFN but enhances the IFN-induced expression of CXCL10 and CXCL11. Luciferase reporter assays revealed a requirement of intact NFκB-binding sites for ZNF395 to stimulate the CXCL10 promoter. The transcriptional activation of CXCL10 and CXCL11 by ZNF395 was abolished after inhibition of IKK by BMS-345541, which increased the stability of ZNF395. ZNF395 encodes at least two motifs that mediate the enhanced degradation of ZNF395 in response to IKK activation. Thus, IKK is required for ZNF395-mediated activation of transcription and enhances its turn-over to keep the activity of ZNF395 low. Our results support a previously unrecognized role of ZNF395 in the innate immune response and inflammation.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2lpJpGh
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Objective Outpatient parenteral antimicrobial therapy (OPAT) provides opportunities for improved cost savings, but in the UK, implementation...
-
Abstract Purpose Overcoming the flaws of current data management conditions in head and neck oncology could enable integrated informatio...
-
CBN News Cancer Took Most of His Tongue, but This Pastor Is Still Singing ... CBN News A youth pastor in San Diego, California is not ...
-
A middle-aged poorly controlled diabetic man developed left-sided orbital and facial swelling several days after extraction of a left upper ...
-
Related Articles Audiologic and radiologic findings in cochlear hypoplasia. Auris Nasus Larynx. 2017 Jan 10;: Authors: Cinar BC, Bat...
-
Universal newborn hearing screening (UNHS) has become the standard of care in many countries. The aim of this study was to evaluate the resu...
-
The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of lichen sclerosus (LS)...
-
Abstract The head-mounted display (HMD) has the potential to improve the quality of ultrasound-guided procedures. The aim of this non-clin...
-
http://ift.tt/2pnwWaQ
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου