TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes.
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2012
|
| _version_ | 1797090059208359936 |
|---|---|
| author | Brenner, C Simmonds, R Wood, S Rose, V Feldmann, M Turner, J |
| author_facet | Brenner, C Simmonds, R Wood, S Rose, V Feldmann, M Turner, J |
| author_sort | Brenner, C |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:13:02Z |
| format | Journal article |
| id | oxford-uuid:b4d7f576-4a27-4fdd-8476-3792be6ab4df |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:13:02Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:b4d7f576-4a27-4fdd-8476-3792be6ab4df2022-03-27T04:29:08ZTLR signalling and adapter utilization in primary human in vitro differentiated adipocytes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b4d7f576-4a27-4fdd-8476-3792be6ab4dfEnglishSymplectic Elements at Oxford2012Brenner, CSimmonds, RWood, SRose, VFeldmann, MTurner, JToll-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. |
| spellingShingle | Brenner, C Simmonds, R Wood, S Rose, V Feldmann, M Turner, J TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes. |
| title | TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes. |
| title_full | TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes. |
| title_fullStr | TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes. |
| title_full_unstemmed | TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes. |
| title_short | TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes. |
| title_sort | tlr signalling and adapter utilization in primary human in vitro differentiated adipocytes |
| work_keys_str_mv | AT brennerc tlrsignallingandadapterutilizationinprimaryhumaninvitrodifferentiatedadipocytes AT simmondsr tlrsignallingandadapterutilizationinprimaryhumaninvitrodifferentiatedadipocytes AT woods tlrsignallingandadapterutilizationinprimaryhumaninvitrodifferentiatedadipocytes AT rosev tlrsignallingandadapterutilizationinprimaryhumaninvitrodifferentiatedadipocytes AT feldmannm tlrsignallingandadapterutilizationinprimaryhumaninvitrodifferentiatedadipocytes AT turnerj tlrsignallingandadapterutilizationinprimaryhumaninvitrodifferentiatedadipocytes |