Table 2 SPM profiles in IL-1β stimulated diseased tendon stromal cells incubated in MaR1 and inhibitors of 15-PGDH.

From: Increased 15-PGDH expression leads to dysregulated resolution responses in stromal cells from patients with chronic tendinopathy

DHA bioactive metabolome

Q1

Q3

Tendon stromal cells Lipid mediators levels (pg/incubation)

Disease + IL-1β

Disease + IL-1β + MaR1

Disease + IL-1β + Indo

Disease + IL-1β + MaR1 + Indo

Disease + IL-1β + SW033291

Disease + IL-1β + MaR1 + SW033291

RvD1

375

141

0.2 ± 0.2

0.0 ± 0.0

—

—

—

—

RvD2

375

141

0.6 ± 0.4

0.9 ± 0.3

—

—

0.1 ± 0.1

0.2 ± 0.2

RvD3

375

147

0.3 ± 0.3

0.4 ± 0.4

—

—

—

—

RvD4

375

101

1.3 ± 1.3

0.5 ± 0.3

—

—

—

—

RvD5

359

199

34.0 ± 3.8

32.9 ± 7.1

1.3 ± 1.3**

0.3 ± 0.3**

8.6 ± 1.2**

7.1 ± 1.6

RvD6

359

101

14.9 ± 2.5

13.5 ± 2.3

4.1 ± 0.5**

7.4 ± 1.1**

3.1 ± 1.3**

2.0 ± 0.4

17R-RvD1

375

141

1.2 ± 0.7

0.6 ± 0.2

—

0.2 ± 0.2

—

0.1 ± 0.1

17R-RvD3

375

147

2.5 ± 1.5

2.4 ± 0.9

— *

—

—

0.0 ± 0.0

PD1

359

153

7.0 ± 1.1

3.5 ± 0.8*

1.5 ± 1.0 *

0.1 ± 0.1

1.4 ± 0.7**

0.2 ± 0.2

17R-PD1

359

153

0.2 ± 0.1

0.2 ± 0.2

—

0.0 ± 0.0

0.1 ± 0.1

0.6 ± 0.3

10 S,17S-diHDHA

359

153

34.6 ± 5.2

46.8 ± 4.7

0.6 ± 0.6*

1.7 ± 1.7

0.9 ± 0.9 **

0.8 ± 0.8

MaR1

359

221

0.9 ± 0.9

560.3 ± 64.4 **

0.0 ± 0.0

723.4 ± 42.5**$

0.7 ± 0.7

662.3 ± 59.5 **##

MaR2

359

191

0.5 ± 0.3

—

0.7 ± 0.3

1.9 ± 0.2*$

2.1 ± 0.5*

— #

7 S,14S-diHDHA

359

221

32.0 ± 5.2

34.9 ± 1.4

—

28.8 ± 1.9$

—**

—

4 S,14S-diHDHA

359

101

—

—

—

—

—

—

14-oxo-MaR1

357

248

0.3 ± 0.2

18.1 ± 2.9 **

0.3 ± 0.2

11.0 ± 0.9 ** $

0.2 ± 0.2

7.6 ± 0.8 **#

n-3 DPA bioactive metabolome

RvD1n-3 DPA

377

143

3.2 ± 1.9

3.4 ± 0.8

0.1 ± 0.1

1.2 ± 0.6

—

0.5 ± 0.5

RvD2n-3 DPA

377

261

0.4 ± 0.3

0.3 ± 0.3

—

0.0 ± 0.0

—

—

RvD5n-3 DPA

361

263

25.4 ± 1.7

13.4 ± 2.5

— **

0.7 ± 0.7 **

— **

— **

PD1n-3 DPA

361

183

0.9 ± 0.5

1.3 ± 0.3

0.4 ± 0.4

1.5 ± 0.1

4.2 ± 1.8

0.7 ± 0.4

10 S,17S-diHDPA

361

183

16.8 ± 1.7

16.7 ± 2.3

5.2 ± 1.3 *

5.1 ± 1.3

3.3 ± 0.5 **

3.5 ± 0.7 **

MaR1n-3 DPA

361

249

3.9 ± 2.1

0.5 ± 0.2

0.4 ± 0.4

1.5 ± 1.5

0.1 ± 0.1

0.1 ± 0.1

EPA bioactive metabolome

RvE1

349

195

—

—

—

0.2 ± 0.0 $

—**

0.2 ± 0.1

RvE2

333

199

49.0 ± 11.7

31.8 ± 2.4

18.9 ± 2.0 *

15.8 ± 3.5

23.6 ± 4.0 *

12.5 ± 1.4 *#

RvE3

333

201

0.4 ± 0.3

0.5 ± 0.3

—

—

—

—

AA bioactive metabolome

LXA4

351

217

—

—

—

—

—

—

LXB4

351

221

1.4 ± 1.4

17.2 ± 17.2

—

3.1 ± 3.1

—

—

5 S,15S-diHETE

335

235

121.8 ± 14.8

750.1 ± 203.5*

—*

—*

—**

—**

15epi-LXA4

351

217

—

—

—

—

—

—

15epi-LXB4

351

221

35.0 ± 7.3

69.8 ± 12.1*

18.5 ± 3.6*

33.8 ± 5.3$

—**

—**

15-oxo-LXA4

349

233

—

0.1 ± 0.1

—

—

0.1 ± 0.0

0.1 ± 0.1

LTB4

335

195

—

—

—

   

5 S,12S-diHETE

335

195

45.6 ± 45.6

36.4 ± 18.3

—

—

—

 

PGD2

351

189

50.0 ± 4.0

34.0 ± 9.5

0.7 ± 0.7**

0.7 ± 0.7**

1.2 ± 1.2**

1.0 ± 1.0**

PGE2

351

189

1655.4 ± 108.7

1275.0 ± 95.0 *

4.6 ± 3.6**

8.9 ± 1.9**

154.5 ± 14.8**

103.0 ± 14.4**#

PGF2α

353

193

258.1 ± 26.0

400.7 ± 138.5

—**

**

2.4 ± 2.2**

3.3 ± 1.9**

TxB2

369

169

374.8 ± 31.5

554.3 ± 191.6

—**

—**

3.3 ± 3.0**

8.3 ± 0.6**

  1. Tendon stromal cells (60,000 cells per well) were derived from diseased supraspinatus tendons. Cells were incubated for 24 h (37 °C) with indomethacin (indo; 10 µM), SW033291 (25 µM) or vehicle (2 h, 37 °C), then with MaR1 (10 nM) or vehicle (24 h 37 °C) and with IL-1β (37 °C; 24 h). Incubations were quenched using ice-cold methanol containing deuterium labelled internal standards and lipid mediators (LM) were identified and quantified using LM-profiling (see methods for details). Q1, M-H (parent ion) and Q3, diagnostic ion in the MS-MS (daughter ion). Results are expressed as pg/incubation. Mean ± SEM of n = 3 per incubation. *P < 0.05, **P < 0.01 vs Disease + IL1β incubations. $P < 0.05, $ $P < 0.01 vs Disease + IL1β  + Indo; #P < 0.05, ##P < 0.01 vs Disease + IL1β  + SW. The detection limit was ~0.1 pg. -, Below levels found in media alone.
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