Effects of type 2 cytokines on glomerular epithelial cells.
Visceral glomerular epithelial cells (GECs) are involved in the maintenance of the filtration barrier and may play a role in immune responses. Cytokines may act on GECs and we wished to test this in vitro. Vascular endothelial growth factor (VEGF) is a specific product of the GEC that may play a role in glomerular permeability. We have investigated whether GECs in culture express receptors for interleukin (IL)-4, 10 and 13 (often grouped together as type 2 cytokines) and whether these cytokines alter GEC VEGF production. Type 2 cytokines were compared to transforming growth factor-beta (TGF-beta) and IL-1beta which are known to upregulate VEGF production. GECs were grown from human nephrectomy specimens and cultured with and without the addition of exogenous cytokines. Messenger RNA data demonstrated the presence of IL-4 receptor alpha, IL-10 receptor 1 and 2, and IL-13 receptors alpha1 and alpha2. However, at the protein level by flow cytometry, only IL-13 alpha2 could be consistently demonstrated. IL-4, IL-10 and IL-13 inhibited production of VEGF but did not affect the pattern of isoform expression. In contrast, TBF-beta and IL-1beta caused an increase in VEGF production. These effects were not explained by effects on proliferation. Our data provide evidence that GECs express receptors for type 2 cytokines and that these cytokines can act directly on GECs, to decrease VEGF production.
Parry
R G
RG
Academic Renal Unit, Southmead Hospital, Bristol, UK. robparry44@yahoo.co.uk
Gillespie
K M
KM
Mathieson
P W
PW
D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000032:analysis; D053701:Receptors, Interleukin-10; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016207:Cytokines; D016228:Endothelial Growth Factors; C508181:IL13RA1 protein, human; D007375:Interleukin-1; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D008222:Lymphokines; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016753:Interleukin-10; D015847:Interleukin-4