Knockout of the neonatal Fc receptor in cultured podocytes alters IL-6 signaling and the actin cytoskeleton.
Am J Physiol Cell Physiol
; 317(5): C1048-C1060, 2019 11 01.
Article
en En
| MEDLINE
| ID: mdl-31553647
ABSTRACT
The neonatal Fc receptor (FcRn) has been shown to be required for antigen presentation in dendritic cells, and global knockout of FcRn attenuates immune-mediated kidney disease. Podocytes express interleukin-6 (IL-6) receptor and produce IL-6 under proinflammatory conditions. Here we examined the role of FcRn in the IL-6-mediated inflammatory response in podocytes. We examined IL-6 production by ELISA and expression by qPCR in wild type (WT) and FcRn knockout (KO) podocytes after treatment with proinflammatory stimuli as well as IL-6-mediated signaling via the JAK/STAT pathway. We also examined podocyte motility in cultured WT and KO podocytes after a proinflammatory challenge. We found that FcRn KO podocytes produced minimal amount of IL-6 after treatment with albumin, IgG, or immune complexes whereas WT podocytes had a robust response. FcRn KO podocytes also had minimal expression of IL-6 compared with WT. By Western blotting, there was significantly less phosphorylated STAT3 in KO podocytes after treatment with IFNγ or immune complexes. In a scratch assay, FcRn KO podocytes showed increased motility comparted KO, suggesting a defect in actin dynamics. Cultured FcRn KO podocytes also demonstrated abnormal stress fibers compared with WT and the defect could be rescued by IL-6 treatment. This study shows that in podocytes, FcRn modulates the IL-6 mediated response to proinflammatory stimuli and regulates podocytes actin structure, motility and synaptopodin expression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Citoesqueleto de Actina
/
Receptores Fc
/
Transducción de Señal
/
Interleucina-6
/
Podocitos
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Asunto de la revista:
FISIOLOGIA
Año:
2019
Tipo del documento:
Article