University of Surrey

Test tubes in the lab Research in the ATI Dance Research

TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes.

Brenner, C, Simmonds, RE, Wood, S, Rose, V, Feldmann, M and Turner, J (2012) TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes. Scand J Immunol, 76 (4). pp. 359-370.

[img] Text (licence)
SRI_deposit_agreement.pdf
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (33kB)
[img] Text
ScanJ adipos signalling.pdf - ["content_typename_Published version (Publisher's proof or final PDF)" not defined]
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (794kB)

Abstract

Toll-like receptors (TLRs) are central to innate immunity and yet their expression is widespread and not restricted to professional inflammatory cells. TLRs have been reported on adipocytes and have been implicated in obesity-associated pathologies such as diabetes. Why TLRs are found on adipocytes is not clear although one hypothesis is that they may coordinate energy utilization for the energy intensive process of an immune response. We have explored TLR signalling in primary human in vitro differentiated adipocytes and investigated the specific adapter molecules that are involved. Only lipopolysaccharide (LPS), poly(I:C), Pam3CSK4 and MALP-2 could induce the production of IL-6, IL-8 and MCP-1 by adipocytes. Poly(I:C) alone caused a strong induction of type I interferons, as assessed by IP-10 production. Using siRNA, it was confirmed that LPS-dependent signalling in adipocytes occurs via TLR4 utilizing the adapter molecules MyD88, Mal and TRIF and caused rapid degradation of IκBα. Pam3CSK4 signalling utilized TLR2, MyD88 and Mal (but not TRIF). However, the response to poly(I:C) observed in these cells appeared not to require TRIF, but MyD88 was required for induction of NFκB-dependent cytokines by Poly(I:C). Despite this, IκBα degradation could not be detected in poly(I:C) stimulated adipocytes at any time-point up to 4 h. Indeed, IL-6 transcription was not induced until 8-16 h after exposure. These data suggest that Pam3CSK4 and LPS signal via the expected routes in human adipocytes, whereas poly(I:C)/TLR3 signalling may act via a TRIF-independent, MyD88-dependent route.

Item Type: Article
Authors :
NameEmailORCID
Brenner, CUNSPECIFIEDUNSPECIFIED
Simmonds, REUNSPECIFIEDUNSPECIFIED
Wood, SUNSPECIFIEDUNSPECIFIED
Rose, VUNSPECIFIEDUNSPECIFIED
Feldmann, MUNSPECIFIEDUNSPECIFIED
Turner, JUNSPECIFIEDUNSPECIFIED
Date : October 2012
Identification Number : 10.1111/j.1365-3083.2012.02744.x
Uncontrolled Keywords : Adaptor Proteins, Vesicular Transport, Adipocytes, Cell Differentiation, Chemokine CCL2, Gene Expression Regulation, Humans, I-kappa B Proteins, Interleukin-6, Interleukin-8, Lipopeptides, Lipopolysaccharides, Myeloid Differentiation Factor 88, Poly I-C, Primary Cell Culture, Protein Isoforms, RNA, Small Interfering, Signal Transduction, Toll-Like Receptors
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 10:55
Last Modified : 31 Oct 2017 17:40
URI: http://epubs.surrey.ac.uk/id/eprint/808582

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800