Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1
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Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1. / Bernhardt, Anja; Fehr, Alexander; Brandt, Sabine; Jerchel, Saskia; Ballhause, Tobias M; Philipsen, Lars; Stolze, Saskia; Geffers, Robert; Weng, Honglei; Fischer, Klaus-Dieter; Isermann, Berend; Brunner-Weinzierl, Monika C; Batra, Arvind; Siegmund, Britta; Zhu, Cheng; Lindquist, Jonathan A; Mertens, Peter R.
In: KIDNEY INT, Vol. 92, No. 5, 11.2017, p. 1157-1177.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1
AU - Bernhardt, Anja
AU - Fehr, Alexander
AU - Brandt, Sabine
AU - Jerchel, Saskia
AU - Ballhause, Tobias M
AU - Philipsen, Lars
AU - Stolze, Saskia
AU - Geffers, Robert
AU - Weng, Honglei
AU - Fischer, Klaus-Dieter
AU - Isermann, Berend
AU - Brunner-Weinzierl, Monika C
AU - Batra, Arvind
AU - Siegmund, Britta
AU - Zhu, Cheng
AU - Lindquist, Jonathan A
AU - Mertens, Peter R
N1 - Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
PY - 2017/11
Y1 - 2017/11
N2 - Tubular cells recruit monocytic cells in inflammatory tubulointerstitial kidney diseases. The cell-cell communication that establishes pro- or anti-inflammatory activities is mainly influenced by cytokines, reactive oxygen species, nitric oxide, and phagocytosis. Key proteins orchestrating these processes such as cold-shock proteins linked with chemoattraction and cell maturation have been identified. The prototypic member of the cold-shock protein family, Y-box binding protein (YB)-1, governs specific phenotypic alterations in monocytic cells and was explored in the present study. Following tubulointerstitial injury by unilateral ureteral obstruction, increased inflammatory cell infiltration and tubular cell CCL5 expression was found in conditional Ybx1 knockout animals with specific depletion in monocytes/macrophages (YB-1ΔLysM). Furthermore, YB-1ΔLysM mice exhibit enhanced tissue damage, myofibroblast activation, and fibrosis. To investigate relevant molecular mechanism(s), we utilized bone marrow-derived macrophage cultures and found that YB-1-deficient macrophages display defects in cell polarization and function, including reduced proliferation and nitric oxide production, loss of phagocytic activity, and failure to upregulate IL-10 and CCL5 expression in response to inflammatory stimuli. Co-culture with primary tubular cells confirmed these findings. Thus, monocytic YB-1 has prominent and distinct roles for cellular feed-forward crosstalk and resolution of inflammatory processes by its ability to regulate cell differentiation and cytokine/chemokine synthesis.
AB - Tubular cells recruit monocytic cells in inflammatory tubulointerstitial kidney diseases. The cell-cell communication that establishes pro- or anti-inflammatory activities is mainly influenced by cytokines, reactive oxygen species, nitric oxide, and phagocytosis. Key proteins orchestrating these processes such as cold-shock proteins linked with chemoattraction and cell maturation have been identified. The prototypic member of the cold-shock protein family, Y-box binding protein (YB)-1, governs specific phenotypic alterations in monocytic cells and was explored in the present study. Following tubulointerstitial injury by unilateral ureteral obstruction, increased inflammatory cell infiltration and tubular cell CCL5 expression was found in conditional Ybx1 knockout animals with specific depletion in monocytes/macrophages (YB-1ΔLysM). Furthermore, YB-1ΔLysM mice exhibit enhanced tissue damage, myofibroblast activation, and fibrosis. To investigate relevant molecular mechanism(s), we utilized bone marrow-derived macrophage cultures and found that YB-1-deficient macrophages display defects in cell polarization and function, including reduced proliferation and nitric oxide production, loss of phagocytic activity, and failure to upregulate IL-10 and CCL5 expression in response to inflammatory stimuli. Co-culture with primary tubular cells confirmed these findings. Thus, monocytic YB-1 has prominent and distinct roles for cellular feed-forward crosstalk and resolution of inflammatory processes by its ability to regulate cell differentiation and cytokine/chemokine synthesis.
KW - Animals
KW - Cell Communication
KW - Cell Differentiation
KW - Chemokine CCL5/metabolism
KW - Coculture Techniques
KW - DNA-Binding Proteins/genetics
KW - Disease Models, Animal
KW - Disease Progression
KW - Female
KW - Fibrosis
KW - Humans
KW - Interleukin-10/metabolism
KW - Kidney Tubules/cytology
KW - Macrophages
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Monocytes/metabolism
KW - Myofibroblasts/metabolism
KW - Nephritis, Interstitial/pathology
KW - Primary Cell Culture
U2 - 10.1016/j.kint.2017.03.035
DO - 10.1016/j.kint.2017.03.035
M3 - SCORING: Journal article
C2 - 28610763
VL - 92
SP - 1157
EP - 1177
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 5
ER -