Expression of functional CCR and CXCR chemokine receptors in podocytes
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Expression of functional CCR and CXCR chemokine receptors in podocytes. / Huber, Tobias Bruno; Reinhardt, Hans Christian; Exner, Markus; Burger, Jan Andreas; Kerjaschki, Dontscho; Saleem, Moin A; Pavenstädt, Hermann.
In: J IMMUNOL, Vol. 168, No. 12, 15.06.2002, p. 6244-52.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Expression of functional CCR and CXCR chemokine receptors in podocytes
AU - Huber, Tobias Bruno
AU - Reinhardt, Hans Christian
AU - Exner, Markus
AU - Burger, Jan Andreas
AU - Kerjaschki, Dontscho
AU - Saleem, Moin A
AU - Pavenstädt, Hermann
PY - 2002/6/15
Y1 - 2002/6/15
N2 - Chemokines and their receptors play an important role in the pathogenesis of acute and chronic glomerular inflammation. However, their expression pattern and function in glomerular podocytes, the primary target cells in a variety of glomerulopathies, have not been investigated as of yet. Using RT-PCR, we now demonstrate the expression of CCR4, CCR8, CCR9, CCR10, CXCR1, CXCR3, CXCR4, and CXCR5 in cultured human podocytes. Stimulation of these receptors induced a concentration-dependent biphasic increase of the free cytosolic calcium concentration in podocytes in culture. In addition, we demonstrate that podocytes release IL-8 in the presence of FCS and that IL-8 down-regulates cell surface CXCR1. Chemokine stimulation of the detected CCRs and CXCRs increased activity of NADPH-oxidase, the primary source of superoxide anions in podocytes. Immunohistochemistry studies revealed only diffuse and weak CXCR expression in healthy human glomerula. In contrast, in membranous nephropathy, a characteristic podocyte disorder, the expression of CXCR1, CXCR3, and CXCR5 is up-regulated in podocytes. In conclusion, podocytes in culture and podocytes in human kidney sections express a set of chemokine receptors. The release of oxygen radicals that accompanies the activation of CCRs and CXCRs may contribute to podocyte injury and the development of proteinuria during membranous nephropathy.
AB - Chemokines and their receptors play an important role in the pathogenesis of acute and chronic glomerular inflammation. However, their expression pattern and function in glomerular podocytes, the primary target cells in a variety of glomerulopathies, have not been investigated as of yet. Using RT-PCR, we now demonstrate the expression of CCR4, CCR8, CCR9, CCR10, CXCR1, CXCR3, CXCR4, and CXCR5 in cultured human podocytes. Stimulation of these receptors induced a concentration-dependent biphasic increase of the free cytosolic calcium concentration in podocytes in culture. In addition, we demonstrate that podocytes release IL-8 in the presence of FCS and that IL-8 down-regulates cell surface CXCR1. Chemokine stimulation of the detected CCRs and CXCRs increased activity of NADPH-oxidase, the primary source of superoxide anions in podocytes. Immunohistochemistry studies revealed only diffuse and weak CXCR expression in healthy human glomerula. In contrast, in membranous nephropathy, a characteristic podocyte disorder, the expression of CXCR1, CXCR3, and CXCR5 is up-regulated in podocytes. In conclusion, podocytes in culture and podocytes in human kidney sections express a set of chemokine receptors. The release of oxygen radicals that accompanies the activation of CCRs and CXCRs may contribute to podocyte injury and the development of proteinuria during membranous nephropathy.
KW - Calcium
KW - Cations, Divalent
KW - Cell Line, Transformed
KW - Cells, Cultured
KW - Cytosol
KW - Fluorescent Antibody Technique
KW - Glomerulonephritis, Membranous
KW - Humans
KW - Immunohistochemistry
KW - Interleukin-8
KW - Kidney Glomerulus
KW - Ligands
KW - RNA, Messenger
KW - Receptors, CXCR3
KW - Receptors, CXCR4
KW - Receptors, CXCR5
KW - Receptors, Chemokine
KW - Receptors, Cytokine
KW - Receptors, Interleukin-8A
KW - Receptors, Interleukin-8B
KW - Serum Albumin, Bovine
KW - Superoxides
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - SCORING: Journal article
C2 - 12055238
VL - 168
SP - 6244
EP - 6252
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 12
ER -