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Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue

Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue
Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue
Background:

Chronically elevated interleukin-6 (IL-6) is implicated in obesity-associated pathologies, where a proportion of this cytokine is derived from adipose tissue. Proinflammatory prostaglandins, which regulate this cytokine elsewhere, are also produced by this tissue.

Objective:

To investigate whether constitutively active cyclooxygenase (COX)/prostaglandin (PG) pathway in white adipose tissue (WAT) is responsible for basal IL-6 production.

Design:

The effect of acetylsalicylic acid (ASA), an inhibitor of COX, on IL-6 was assessed in human subjects and mice. COX, downstream PG synthase (PGS) activity and PG receptor signalling were determined in subcutaneous (SC), gonadal (GN) WAT and adipocytes.

Methods and Results:

In obese humans, low-dose ASA (150 mg day−1 for 10 days) inhibited systemic IL-6 and reduced IL-6 release from SC WAT ex vivo (0.2 mM). Similarly, in mice, ASA (0.2 and 2.0 mg kg−1) suppressed SC WAT 6-keto-PGF1α (a stable metabolite of prostacyclin) and IL-6 release. Although both COX isoforms are comparably expressed, prostacyclin synthase expression is higher in GN WAT, with levels of activity correlating directly with IL-6. Both ASA (5 mM) and NS-398 (COX-2 selective inhibitor ⩽1 μM), but not SC-560 (COX-1 selective inhibitor ⩽1 μM), attenuated IL-6 release from murine WAT in vitro and abolished its depot differences. Prostacyclin receptor (IP) and, to a lesser extent, PGE2 (EP2 and EP4) receptor agonists elevated the release of IL-6 from adipocytes.

Conclusions:

In adipose tissue, constitutive COX-2-coupled prostacyclin triggers the release of basal IL-6, which in obese subjects is significantly dampened by ASA ingestion, thus offering a novel, modifiable pathway to regulate the potentially pathological component of this cytokine.
0307-0565
1807-1815
Ogston, N.C.
bc7c6da9-4fbb-43d8-aa8a-7be7334ca16d
Karastergiou, K.
4d30c8f7-130b-4202-9b1f-f432c66f5987
Hosseinzadeh-Attar, M.J.
e18dcf11-2ba0-4cfb-8926-594e69199fd5
Bhome, R.
d7b1e0d3-5925-460a-871d-5f52f69c649b
Madani, R.
2b9a818d-9234-4dd5-8184-017432cce7e8
Stables, M.
379b7099-d36a-4ad3-b5f1-5d72af3a8f70
Gilroy, D.
500cc92b-c054-4854-9b0e-d9d2b561f773
Flachs, P.
e09b9f27-ebd3-4b26-871d-878f79b45b88
Hensler, M.
0dbf80e2-8057-42a6-8dea-bcc3282849f9
Kopecky, J.
a3d4436f-43a9-4220-aabf-bf80200e009e
Mohamed-Ali, V.
a681cb9a-deee-43e7-8cff-42219891ca96
Ogston, N.C.
bc7c6da9-4fbb-43d8-aa8a-7be7334ca16d
Karastergiou, K.
4d30c8f7-130b-4202-9b1f-f432c66f5987
Hosseinzadeh-Attar, M.J.
e18dcf11-2ba0-4cfb-8926-594e69199fd5
Bhome, R.
d7b1e0d3-5925-460a-871d-5f52f69c649b
Madani, R.
2b9a818d-9234-4dd5-8184-017432cce7e8
Stables, M.
379b7099-d36a-4ad3-b5f1-5d72af3a8f70
Gilroy, D.
500cc92b-c054-4854-9b0e-d9d2b561f773
Flachs, P.
e09b9f27-ebd3-4b26-871d-878f79b45b88
Hensler, M.
0dbf80e2-8057-42a6-8dea-bcc3282849f9
Kopecky, J.
a3d4436f-43a9-4220-aabf-bf80200e009e
Mohamed-Ali, V.
a681cb9a-deee-43e7-8cff-42219891ca96

Ogston, N.C., Karastergiou, K., Hosseinzadeh-Attar, M.J., Bhome, R., Madani, R., Stables, M., Gilroy, D., Flachs, P., Hensler, M., Kopecky, J. and Mohamed-Ali, V. (2008) Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue. International Journal of Obesity, 32 (12), 1807-1815. (doi:10.1038/ijo.2008.190).

Record type: Article

Abstract

Background:

Chronically elevated interleukin-6 (IL-6) is implicated in obesity-associated pathologies, where a proportion of this cytokine is derived from adipose tissue. Proinflammatory prostaglandins, which regulate this cytokine elsewhere, are also produced by this tissue.

Objective:

To investigate whether constitutively active cyclooxygenase (COX)/prostaglandin (PG) pathway in white adipose tissue (WAT) is responsible for basal IL-6 production.

Design:

The effect of acetylsalicylic acid (ASA), an inhibitor of COX, on IL-6 was assessed in human subjects and mice. COX, downstream PG synthase (PGS) activity and PG receptor signalling were determined in subcutaneous (SC), gonadal (GN) WAT and adipocytes.

Methods and Results:

In obese humans, low-dose ASA (150 mg day−1 for 10 days) inhibited systemic IL-6 and reduced IL-6 release from SC WAT ex vivo (0.2 mM). Similarly, in mice, ASA (0.2 and 2.0 mg kg−1) suppressed SC WAT 6-keto-PGF1α (a stable metabolite of prostacyclin) and IL-6 release. Although both COX isoforms are comparably expressed, prostacyclin synthase expression is higher in GN WAT, with levels of activity correlating directly with IL-6. Both ASA (5 mM) and NS-398 (COX-2 selective inhibitor ⩽1 μM), but not SC-560 (COX-1 selective inhibitor ⩽1 μM), attenuated IL-6 release from murine WAT in vitro and abolished its depot differences. Prostacyclin receptor (IP) and, to a lesser extent, PGE2 (EP2 and EP4) receptor agonists elevated the release of IL-6 from adipocytes.

Conclusions:

In adipose tissue, constitutive COX-2-coupled prostacyclin triggers the release of basal IL-6, which in obese subjects is significantly dampened by ASA ingestion, thus offering a novel, modifiable pathway to regulate the potentially pathological component of this cytokine.

Full text not available from this repository.

More information

e-pub ahead of print date: 4 November 2008
Published date: 2008

Identifiers

Local EPrints ID: 415663
URI: https://eprints.soton.ac.uk/id/eprint/415663
ISSN: 0307-0565
PURE UUID: 5234f2b9-f2c9-432e-8068-788c70180363

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Date deposited: 17 Nov 2017 17:30
Last modified: 13 Mar 2019 19:14

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Contributors

Author: N.C. Ogston
Author: K. Karastergiou
Author: M.J. Hosseinzadeh-Attar
Author: R. Bhome
Author: R. Madani
Author: M. Stables
Author: D. Gilroy
Author: P. Flachs
Author: M. Hensler
Author: J. Kopecky
Author: V. Mohamed-Ali

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