Exposure to pollutants, such as ozone, exacerbates airway inflammation and hyperresponsiveness (AHR). TNF-stimulated gene 6 (TSG-6) is required to transfer inter-α-inhibitor heavy chains (HC) to hyaluronan (HA), facilitating HA receptor binding. TSG-6 is necessary for AHR in allergic asthma, because it facilitates the development of a pathological HA–HC matrix. However, the role of TSG-6 in acute airway inflammation is not well understood. Here, we hypothesized that TSG-6 is essential for the development of HA- and ozone-induced AHR. TSG-6−/− and TSG-6+/+ mice were exposed to ozone or short-fragment HA (sHA), and AHR was assayed via flexiVent. The AHR response to sHA was evaluated in the isolated tracheal ring assay in tracheal rings from TSG-6−/− or TSG-6+/+, with or without the addition of exogenous TSG-6, and with or without inhibitors of Rho-associated, coiled-coil–containing protein kinase (ROCK), ERK, or PI3K. Smooth-muscle cells from mouse tracheas were assayed in vitro for signaling pathways. We found that TSG-6 deficiency protects against AHR after ozone (in vivo) or sHA (in vitro and in vivo) exposure. Moreover, TSG-6−/− tracheal ring non-responsiveness to sHA was reversed by exogenous TSG-6 addition. sHA rapidly activated RhoA, ERK, and Akt in airway smooth-muscle cells, but only in the presence of TSG-6. Inhibition of ROCK, ERK, or PI3K/Akt blocked sHA/TSG-6–mediated AHR. In conclusion, TSG-6 is necessary for AHR in response to ozone or sHA, in part because it facilitates rapid formation of HA–HC complexes. The sHA/TSG-6 effect is mediated by RhoA, ERK, and PI3K/Akt signaling.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2zfisue
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
-
Dtsch med Wochenschr DOI: 10.1055/s-0043-100054 Hintergrund und Fragestellung Ein etablierter Weg, die optimale Behandlung von Tumorpatien...
-
Antibodies, Vol. 9, Pages 21: Construction of Ant... In Vivo and In Vitro Evaluation of Bull Semen Pro... Vertebral artery fenestration mimi...
-
Abstract Purpose F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is emerging to be a useful tool in supporting the diag...
-
Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
-
Publication date: December 2017 Source: Advances in Biological Regulation, Volume 66 Author(s): Lauren Rusnak, Haian Fu The mitogen-activ...
-
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, Butyric Acid from Probiotic Staphyloco...
-
Correction to: The IL-23p19/EBI3 heterodimeric cytokine termed IL-39 remains a theoretical cytokine in man The original article can be found...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου