Toll-like receptor 3 and 4 signalling through the TRIF and TRAM adaptors in haematopoietic cells promotes atherosclerosis

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: (WFRF:(Akira S.)) > (2010-2014) > Toll-like receptor ...

Details
MARC

Lundberg, A. M. (author)

Toll-like receptor 3 and 4 signalling through the TRIF and TRAM adaptors in haematopoietic cells promotes atherosclerosis

Article/chapterEnglish2013

Publisher, publication year, extent ...

2013-02-14
Oxford University Press (OUP),2013

Numbers

LIBRIS-ID:oai:gup.ub.gu.se/179569
https://gup.ub.gu.se/publication/179569URI
https://doi.org/10.1093/cvr/cvt033DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:126911568URI

Supplementary language notes

Language:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

AIMS: Members of the Toll-like receptor (TLR) family initiate innate immune responses and were recently shown to play a role in atherosclerosis. However, the mechanisms that link TLR ligation to vascular inflammation and atherogenesis remain unclear. To identify which signalling pathways downstream of TLRs in immune cells are pro-atherogenic, we analysed the role of the TLR-specific adaptors MyD88 adaptor-like (MAL), TRIF-related adaptor molecule (TRAM), and TIR-domain-containing adaptor-inducing interferon-beta (TRIF) in atherosclerosis. METHODS AND RESULTS: Using a bone-marrow transplantation strategy into low-density lipoprotein receptor-deficient (Ldlr-/-) mice, we could specifically study the absence of the TLR adaptors in immune cells. We showed that haematopoietic deficiency of TRAM and TRIF, but not MAL, reduces atherosclerosis without affecting cholesterol metabolism. This was mediated by decreased aortic inflammation, indicated by lower aortic levels of pro-inflammatory mediators, and reduced influx of macrophages and T cells. Furthermore, by studying Tlr3-/- chimeric Ldlr-/- mice, we found that deleting TLR3 in immune cells significantly reduced both aortic inflammation and atherosclerotic burden. CONCLUSIONS: By studying hypercholesterolaemic mice with defects in TLR-signalling adaptors, we demonstrated that deleting either TRAM or TRIF in immune cells is sufficient to attenuate vessel inflammation and protect against atherosclerosis. In addition, these adaptors elicit partly different sets of inflammatory mediators and can independently inhibit the disease process. Furthermore, we identify TLR3 as a pro-atherogenic receptor in haematopoietic immune cells. The identification of these pro-atherogenic pathways downstream of TLR3 and TLR4 contributes to a better understanding of TLRs and their signalling pathways in the pathogenesis of atherosclerosis.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Annan medicin och hälsovetenskap hsv//swe
MEDICAL AND HEALTH SCIENCES Other Medical and Health Sciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
Atherosclerosis TRAM TRIF TLR3 Vascular inflammation

Added entries (persons, corporate bodies, meetings, titles ...)

Ketelhuth, D. F.Karolinska Institutet (author)
Johansson, Maria E,1977Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xjmarw (author)
Gerdes, N. (author)
Liu, S. (author)
Yamamoto, M. (author)
Akira, S. (author)
Hansson, G. K.Karolinska Institutet (author)
Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för fysiologi (creator_code:org_t)

Related titles

In:Cardiovascular Research: Oxford University Press (OUP)99:2, s. 364-3730008-63631755-3245

Internet link

Find in a library

Cardiovascular Research (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Lundberg, A. M.; Ketelhuth, D. F.; Johansson, Maria ...; Gerdes, N.; Liu, S.; Yamamoto, M.; show more...; Akira, S.; Hansson, G. K.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Other Medical an ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

Articles in the publication: Cardiovascular R ...

By the university: University of Gothenburg; Karolinska Institutet

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se