Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Lanosterol Synthase Regul… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Lanosterol Synthase Regulates Human Rhinovirus Replication in Human Bronchial Epithelial Cells

Artikel i vetenskaplig tidskrift
Författare Cristopher McCrae
A. Dzgoev
Marcus Ståhlman
J. Horndahl
R. Svard
A. Grosse
T. Grosskopf
M. A. Skujat
N. Williams
S. Schubert
C. Echeverri
C. Jackson
A. Guedan
R. Solari
O. Vaarala
M. Kraan
Madeleine Rådinger
Publicerad i American Journal of Respiratory Cell and Molecular Biology
Volym 59
Nummer/häfte 6
Sidor 713-722
ISSN 1044-1549
Publiceringsår 2018
Publicerad vid Krefting Research Centre
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 713-722
Språk en
Länkar dx.doi.org/10.1165/rcmb.2017-0438OC
Ämnesord rhinovirus, lanosterol synthase, asthma, chronic obstructive pulmonary disease, host-pathogen, respiratory syncytial virus, disease virus, cholesterol, asthma, cyclase, 24(s),25-epoxycholesterol, exacerbations, inhibitors, infection, membrane
Ämneskategorier Lungmedicin och allergi

Sammanfattning

Human rhinovirus (RV) infections are a significant risk factor for exacerbations of asthma and chronic obstructive pulmonary disease. Thus, approaches to prevent RV infection in such patients would give significant benefit. Through RNA interference library screening, we identified lanosterol synthase (LSS), a component of the cholesterol biosynthetic pathway, as a novel regulator of RV replication in primary normal human bronchial epithelial cells. Selective knock down of LSS mRNA with short interfering RNA inhibited RV2 replication in normal human bronchial epithelial cells. Small molecule inhibitors of LSS mimicked the effect of LSS mRNA knockdown in a concentration-dependent manner. We further demonstrated that the antiviral effect is not dependent on a reduction in total cellular cholesterol but requires a 24-hour preincubation with the LSS inhibitor. The rank order of antiviral potency of the LSS inhibitors used was consistent with LSS inhibition potency; however, all compounds showed remarkably higher potency against RV compared with the LSS enzyme potency. We showed that LSS inhibition led to an induction of 24(S),25 epoxycholesterol, an important regulator of the sterol pathway. We also demonstrated that LSS inhibition led to a profound increase in expression of the innate antiviral defense protein, IFN-beta. We found LSS to be a novel regulator of RV replication and innate antiviral immunity and identified a potential molecular mechanism for this effect, via induction of 24(S),25 epoxycholesterol. Inhibition of LSS could therefore be a novel therapeutic target for prevention of RV-induced exacerbations.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?

Denna text är utskriven från följande webbsida:
http://www.gu.se/forskning/publikation/?publicationId=274637
Utskriftsdatum: 2019-09-17