title: In vivo modulation of soluble "antagonistic" IL-6 receptor synthesis and release in ESRD.
abstract: Soluble gp130 (sgp130) is a soluble circulating receptor of IL-6 with "antagonistic" biologic activity. It is generated independently by either shedding of the extracellular domain of membrane gp130 or alternative mRNA splicing. This study was addressed to clarify the mechanisms underlying sgp130 synthesis and release in patients who undergo regular dialysis treatment (RDT) using dialytic membranes with different biocompatibility. Two groups of RDT patients were enrolled: 11 patients who were treated with cellulosic membranes (C) and 10 patients who were treated with synthetic membranes (S). Ten healthy subjects constituted the control group. Serum samples and peripheral blood mononuclear cells (PBMC) were harvested in all groups (before dialysis in RDT patients). PBMC were cultured for 24 h in the absence or presence of LPS. The serum levels of sgp130 were significantly higher in C group than in control and S patients (C, 603.1 +/- 89.9; control, 396 +/- 49.5; S, 423.4 +/- 27.7 ng/ml; P < 0.01). PBMC from C patients, in the absence of any mitogenic stimulation, released a significantly greater amount of sgp130 as compared with S and control groups (C, 532.6 +/- 161.2; S, 332.4 +/- 148.6; control, 341.4 +/- 125.4 pg/ml; P < 0.01). The sgp130 release was positively correlated with the release of both IL-6 (r = 0.336, P < 0.05) and sIL-6R receptor (r = 0.324, P < 0.05). A significantly higher gp130 gene expression was also observed in unstimulated PBMC from C patients when compared with control and S groups. It is interesting that the expression of the 85-bp exon characteristic of the alternative splicing mRNA for sgp130 was low in all groups. Finally, confocal microscopy analysis showed an increased expression of gp130 on cell surface in unstimulated PBMC from C patients as compared with control and S groups. Our results demonstrate that in patients on RDT with C membranes, the synthesis and release of sgp130 "antagonistic" receptor is significantly increased. This release is seemingly due to a shedding of membrane-bound gp130 receptor. The increased sgp130 release may partially counteract the inflammatory effects caused by IL-6.
authors.affiliation: Department of Nephrology, University Federico II of Naples, Via Tasso 91/B, Napoli 80127, Italy. memoli@unina.it
authors.forename: Bruno
authors.initials: B
authors.lastname: Memoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.forename: Michela
authors.initials: M
authors.lastname: Soccio
authors.forename: Loredana
authors.initials: L
authors.lastname: Postiglione
authors.forename: Brunella
authors.initials: B
authors.lastname: Guida
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bisesti
authors.forename: Pasquale
authors.initials: P
authors.lastname: Esposito
authors.forename: Alfredo
authors.initials: A
authors.lastname: Procino
authors.forename: Daniela
authors.initials: D
authors.lastname: Marrone
authors.forename: Ashour
authors.initials: A
authors.lastname: Michael
authors.forename: Michele
authors.initials: M
authors.lastname: Andreucci
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Schena
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pertosa
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D015703:Antigens, CD / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D002482:Cellulose; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008567:Membranes, Artificial; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics; D006435:Renal Dialysis / Q000295:instrumentation; D012995:Solubility
chemical_list: D015703:Antigens, CD; D016207:Cytokines; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D008567:Membranes, Artificial; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D002482:Cellulose