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Podocytes regulate neutrophil recruitment by glomerular endothelial cells via
IL-6-mediated crosstalk
#MMPMID24872191
Kuravi SJ
; McGettrick HM
; Satchell SC
; Saleem MA
; Harper L
; Williams JM
; Rainger GE
; Savage CO
J Immunol
2014[Jul]; 193
(1
): 234-43
PMID24872191
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Stromal cells actively modulate the inflammatory process, in part by influencing
the ability of neighboring endothelial cells to support the recruitment of
circulating leukocytes. We hypothesized that podocytes influence the ability of
glomerular endothelial cells (GEnCs) to recruit neutrophils during inflammation.
To address this, human podocytes and human GEnCs were cultured on opposite sides
of porous inserts and then treated with or without increasing concentrations of
TNF-? prior to addition of neutrophils. The presence of podocytes significantly
reduced neutrophil recruitment to GEnCs by up to 50% when cultures were treated
with high-dose TNF-? (100 U/ml), when compared with GEnC monocultures.
Importantly, this phenomenon was dependent on paracrine actions of soluble IL-6,
predominantly released by podocytes. A similar response was absent when HUVECs
were cocultured with podocytes, indicating a tissue-specific phenomenon.
Suppressor of cytokine signaling 3 elicited the immunosuppressive actions of IL-6
in a process that disrupted the presentation of chemokines on GEnCs by altering
the expression of the duffy Ag receptor for chemokines. Interestingly, suppressor
of cytokine signaling 3 knockdown in GEnCs upregulated duffy Ag receptor for
chemokines and CXCL5 expression, thereby restoring the neutrophil recruitment. In
summary, these studies reveal that podocytes can negatively regulate neutrophil
recruitment to inflamed GEnCs by modulating IL-6 signaling, identifying a
potential novel anti-inflammatory role of IL-6 in renal glomeruli.
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