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2015 | 2 | 1 |

Article title

Peroxisome proliferator-activated receptor α
and γ agonists differently regulate classical and
alternative macrophage activation

Content

Title variants

Languages of publication

EN

Abstracts

EN
Peroxisome proliferator-activated receptor
(PPAR) agonists, fibrates and thiazolidinediones, are
commonly used drugs in the treatment of dyslipidemia and
diabetes. Their targets, PPARα and PPARγ, have also been
shown to have a role in the regulation of inflammatory
responses linking metabolism and inflammation. In
the present study we investigated the effects of PPAR
agonists on macrophage activation. In addition to the
proinflammatory classical activation, we also focused
on interleukin (IL) 4 and 13 -induced alternative
activation which is a significant macrophage phenotype
in tissue repairing processes and in fibrosing diseases.
PPARα agonists GW7647 and fenofibrate as well as PPARγ
agonist GW1929 inhibited lipopolysaccharide-induced
classical macrophage activation and production of the
characteristic biomarkers of this phenotype, i.e. IL-6 and
nitric oxide, in murine J774 macrophages. Remarkably,
the PPARα agonists also inhibited IL-4 and IL-13 –induced
expression of alternative activation markers arginase-1,
fizz1 and mannose receptor 1 whereas the PPARγ agonist
GW1929 enhanced their expression in J774 macrophages.
The PPARα agonists GW7647 and fenofibrate also
attenuated the production of alternative activation
markers chemokine (C-C motif) ligand 13 and plateletderived
growth factor in human THP-1 macrophages.
The present findings show that PPARα and PPARγ agonists
differently regulate classical and alternative macrophage
phenotypes. Furthermore, PPARα activation was
introduced as a novel concept to down-regulate alternative
macrophage activation indicating that PPARα agonists
have therapeutic potential in conditions associated with aberrant alternative macrophage activation such as
fibrosing diseases.

Publisher

Year

Volume

2

Issue

1

Physical description

Dates

received
2 - 3 - 2015
online
21 - 4 - 2015
accepted
23 - 3 - 2015

Contributors

  • The Immunopharmacology
    Research Group, University of Tampere School of Medicine and
    Tampere University Hospital, Tampere, Finland
  • The Immunopharmacology
    Research Group, University of Tampere School of Medicine and
    Tampere University Hospital, Tampere, Finland
author
  • The Immunopharmacology
    Research Group, University of Tampere School of Medicine and
    Tampere University Hospital, Tampere, Finland

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Document Type

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.-psjd-doi-10_1515_immun-2015-0001
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