Synovial microparticles from arthritic patients modulate chemokine and cytokine release by synoviocytes

Table 3 Effect of synovial microparticles on the release of inflammatory mediators by fibroblast-like synoviocytes from arthritic patients (n = 11)

Mediator	Control		P*	MP-free synovial fluid	MP (1×)	N_x/N_t	P ^†	MP (3×)	N_x/N_t	P ^‡
	Unstimulated	IL-1β
MCP-1 (pg/ml)	456	4,754	0.001	469	488	6/11	0.010	900	4/6	0.156
	(355–1,292)	(2,492–6,081)		(293–1,241)	(338–1,481)	higher		(346–2,326)	higher
sICAM-1 (ng/ml)	0.09	0.40	0.007	1.04	2.00	8/11	0.010	6.07	6/6	0.031
	(0–0.3)	(0–0.76)		(0.34–1.84)	(0.35–4.07)	higher		(0.91–11.75)	higher
IL-8 (pg/ml)	0	8,642	0.001	26	301	5/11	0.008	790	6/6	0.031
	(0–564)	(2,954–18,330)		(0–528)	(0–707)	higher		(0–2,100)	higher
IL-6 (pg/ml)	74	4949	0.001	110	136	7/11	0.042	436	6/6	0.031
	(24–1,710)	(1,870–22,797)		(30–1,176)	(34–1,937)	higher		(44–3,766)	higher
VEGF (pg/ml)	48	79	0.014	34	74	10/11	0.001	111	6/6	0.078
	(11–102)	(7–141)		(1–97)	(28–138)	higher		(27–161)	higher
GM-CSF (pg/ml)	32	53	0.004	31	22	10/11	0.002	18	6/6	0.016
	(28–40)	(40–72)		(26–70)	(14–43)	lower		(14–25)	lower
RANTES (pg/ml)	0	138	0.001	0	0.2	4/11	0.031	4.2	5/6	0.062
	(0–74)	(46–277)		(0–58)	(0–86)	higher		(0–32)	higher

Results are medians, with ranges in parentheses. Concentrations of mediators were determined in the culture supernatant of the fibroblast-like synoviocytes (FLS) by ELISA as described in the Materials and methods section. FLS were incubated for 24 hours with 1 ml of culture medium containing 1% FCS (negative control), 975 μl of culture medium supplemented with either (1) 25 μl of interleukin (IL)-1β (final concentration 125 pg/ml; positive control), (2) 25 μl (onefold (1×) or threefold (3×) concentrated) microparticles (MP), or (3) MP-free synovial fluid. P*, positive versus negative control; P^†, MP (1×) versus MP-free synovial fluid; P^‡, MP (3×) versus MP (1×). N_x/N_t, number of individual culture supernatants that contained elevated or decreased concentrations of mediators after incubation for 24 hours with isolated MP compared with MP-free synovial fluid, divided by the number of patients studied. GM-CSF, granulocyte/macrophage colony-stimulating factor; sICAM-1, soluble intracellular adhesion molecule-1; MCP-1, monocyte chemoattractant protein-1; VEGF, vascular endothelial growth factor.

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