15-deoxy-Delta12,14-prostaglandin J2 inhibits INF-gamma-induced JAK/STAT1 signalling pathway activation and IP-10/CXCL10 expression in mesangial cells

Standard

15-deoxy-Delta12,14-prostaglandin J2 inhibits INF-gamma-induced JAK/STAT1 signalling pathway activation and IP-10/CXCL10 expression in mesangial cells. / Panzer, Ulf; Zahner, Gunther; Wienberg, Ulrike; Steinmetz, Oliver M; Peters, Anett; Turner, Jan Eric; Paust, Hans-Joachim; Wolf, Gunter; Stahl, Rolf A K; Schneider, André.

in: NEPHROL DIAL TRANSPL, Jahrgang 23, Nr. 12, 01.12.2008, S. 3776-85.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

APA

Vancouver

Bibtex

@article{149baac893f9408a91ea824d5081421d,
title = "15-deoxy-Delta12,14-prostaglandin J2 inhibits INF-gamma-induced JAK/STAT1 signalling pathway activation and IP-10/CXCL10 expression in mesangial cells",
abstract = "BACKGROUND: Activators of the peroxisome proliferator-activated receptor gamma (PPARgamma), originally found to be implicated in lipid metabolism and glucose homeostasis, have been shown to modulate inflammatory responses through interference with cytokine and chemokine production. Given the central role of mesangial cell-derived chemokines in glomerular leukocyte recruitment in human and experimental glomerulonephritis, we studied the influence of natural and synthetic PPARgamma activators on INF-gamma-induced expression of the T cell-attracting chemokines IP-10/CXCL10, Mig/CXCL9 and I-TAC/CXCL11 in mouse mesangial cells.METHODS: INF-gamma-treated mesangial cells were cultured in the presence or absence of either the naturally occurring PPARgamma ligand 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) or synthetic PPARgamma activators of the glitazone group. Chemokine mRNA and protein expression and activation of the JAK/STAT signalling pathway were analysed.RESULTS: The 15d-PGJ(2), but not synthetic PPARgamma ligands, dose-dependently inhibited INF-gamma-induced chemokine gene (mRNA and protein) expression. Combined results from EMSA and western blot analysis revealed the inhibitory ability of 15d-PGJ(2), but not of synthetic PPARgamma ligands, on IFN-gamma-induced tyrosine phosphorylation of JAK1, JAK2, STAT1 and nuclear STAT1 translocation and DNA binding.CONCLUSIONS: Our results demonstrate that 15d-PGJ(2) inhibits INF-gamma-induced chemokine expression in mesangial cells by targeting the JAK/STAT signalling pathway. This effect is independent of an interference with PPARgamma.",
keywords = "Animals, Cells, Cultured, Chemokine CXCL10, Chemokine CXCL11, Chemokine CXCL9, Chromans, Gene Expression, Glomerulonephritis, Interferon-gamma, Janus Kinases, Mesangial Cells, Mice, PPAR gamma, Prostaglandin D2, RNA, Messenger, Recombinant Proteins, STAT1 Transcription Factor, Signal Transduction, Thiazolidinediones",
author = "Ulf Panzer and Gunther Zahner and Ulrike Wienberg and Steinmetz, {Oliver M} and Anett Peters and Turner, {Jan Eric} and Hans-Joachim Paust and Gunter Wolf and Stahl, {Rolf A K} and Andr{\'e} Schneider",
year = "2008",
month = dec,
day = "1",
doi = "10.1093/ndt/gfn361",
language = "English",
volume = "23",
pages = "3776--85",
journal = "NEPHROL DIAL TRANSPL",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - 15-deoxy-Delta12,14-prostaglandin J2 inhibits INF-gamma-induced JAK/STAT1 signalling pathway activation and IP-10/CXCL10 expression in mesangial cells

AU - Panzer, Ulf

AU - Zahner, Gunther

AU - Wienberg, Ulrike

AU - Steinmetz, Oliver M

AU - Peters, Anett

AU - Turner, Jan Eric

AU - Paust, Hans-Joachim

AU - Wolf, Gunter

AU - Stahl, Rolf A K

AU - Schneider, André

PY - 2008/12/1

Y1 - 2008/12/1

N2 - BACKGROUND: Activators of the peroxisome proliferator-activated receptor gamma (PPARgamma), originally found to be implicated in lipid metabolism and glucose homeostasis, have been shown to modulate inflammatory responses through interference with cytokine and chemokine production. Given the central role of mesangial cell-derived chemokines in glomerular leukocyte recruitment in human and experimental glomerulonephritis, we studied the influence of natural and synthetic PPARgamma activators on INF-gamma-induced expression of the T cell-attracting chemokines IP-10/CXCL10, Mig/CXCL9 and I-TAC/CXCL11 in mouse mesangial cells.METHODS: INF-gamma-treated mesangial cells were cultured in the presence or absence of either the naturally occurring PPARgamma ligand 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) or synthetic PPARgamma activators of the glitazone group. Chemokine mRNA and protein expression and activation of the JAK/STAT signalling pathway were analysed.RESULTS: The 15d-PGJ(2), but not synthetic PPARgamma ligands, dose-dependently inhibited INF-gamma-induced chemokine gene (mRNA and protein) expression. Combined results from EMSA and western blot analysis revealed the inhibitory ability of 15d-PGJ(2), but not of synthetic PPARgamma ligands, on IFN-gamma-induced tyrosine phosphorylation of JAK1, JAK2, STAT1 and nuclear STAT1 translocation and DNA binding.CONCLUSIONS: Our results demonstrate that 15d-PGJ(2) inhibits INF-gamma-induced chemokine expression in mesangial cells by targeting the JAK/STAT signalling pathway. This effect is independent of an interference with PPARgamma.

AB - BACKGROUND: Activators of the peroxisome proliferator-activated receptor gamma (PPARgamma), originally found to be implicated in lipid metabolism and glucose homeostasis, have been shown to modulate inflammatory responses through interference with cytokine and chemokine production. Given the central role of mesangial cell-derived chemokines in glomerular leukocyte recruitment in human and experimental glomerulonephritis, we studied the influence of natural and synthetic PPARgamma activators on INF-gamma-induced expression of the T cell-attracting chemokines IP-10/CXCL10, Mig/CXCL9 and I-TAC/CXCL11 in mouse mesangial cells.METHODS: INF-gamma-treated mesangial cells were cultured in the presence or absence of either the naturally occurring PPARgamma ligand 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) or synthetic PPARgamma activators of the glitazone group. Chemokine mRNA and protein expression and activation of the JAK/STAT signalling pathway were analysed.RESULTS: The 15d-PGJ(2), but not synthetic PPARgamma ligands, dose-dependently inhibited INF-gamma-induced chemokine gene (mRNA and protein) expression. Combined results from EMSA and western blot analysis revealed the inhibitory ability of 15d-PGJ(2), but not of synthetic PPARgamma ligands, on IFN-gamma-induced tyrosine phosphorylation of JAK1, JAK2, STAT1 and nuclear STAT1 translocation and DNA binding.CONCLUSIONS: Our results demonstrate that 15d-PGJ(2) inhibits INF-gamma-induced chemokine expression in mesangial cells by targeting the JAK/STAT signalling pathway. This effect is independent of an interference with PPARgamma.

KW - Animals

KW - Cells, Cultured

KW - Chemokine CXCL10

KW - Chemokine CXCL11

KW - Chemokine CXCL9

KW - Chromans

KW - Gene Expression

KW - Glomerulonephritis

KW - Interferon-gamma

KW - Janus Kinases

KW - Mesangial Cells

KW - Mice

KW - PPAR gamma

KW - Prostaglandin D2

KW - RNA, Messenger

KW - Recombinant Proteins

KW - STAT1 Transcription Factor

KW - Signal Transduction

KW - Thiazolidinediones

U2 - 10.1093/ndt/gfn361

DO - 10.1093/ndt/gfn361

M3 - SCORING: Journal article

C2 - 18596134

VL - 23

SP - 3776

EP - 3785

JO - NEPHROL DIAL TRANSPL

JF - NEPHROL DIAL TRANSPL

SN - 0931-0509

IS - 12

ER -