Interleukin 4 Co-Stimulates the PDGF-BB- and bFGF-Mediated Proliferation of Mesangial Cells and Myofibroblasts

Sommer, Manfred; Eismann, Ulrike; Gerth, Jens; Stein, Günter

doi:10.1159/000065451

Cited by 14 publications

(13 citation statements)

References 32 publications

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“…35,36 In renal cells, IL-6 and IL-4 induce the production of cytokines, chemokines, ECM proteins, and regulate cell growth. 37,38 IL-4 amplifies the response of other cytokines. In tubuloepithelial cells, IL-4 increases CD40-induced RANTES production.…”

Section: Discussionmentioning

confidence: 99%

CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

Sánchez-López¹,

Rayego²,

Rodrigues‐Díez³

et al. 2009

Journal of the American Society of Nephrology

118

100

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Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-B) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-B activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-␥, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-B inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-B pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-B activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-B pathway.

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Section: Discussionmentioning

confidence: 99%

CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

Sánchez-López¹,

Rayego²,

Rodrigues‐Díez³

et al. 2009

Journal of the American Society of Nephrology

118

100

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“…Bovine renal epithelial cells (bEPC) were isolated from kidney cortex as previously described [12, 13]. Briefly, pieces (approx.…”

Section: Methodsmentioning

confidence: 99%

“…The measurement of incorporated radioactivity has been described in detail previously [12]. Briefly, bEPC were seeded into 24-well plates.…”

Section: Methodsmentioning

confidence: 99%

Rosiglitazone Increases PPARγ in Renal Tubular Epithelial Cells and Protects against Damage by Hydrogen Peroxide

Sommer

Wolf²

2007

Am J Nephrol

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Background/Aims: Thiazolidinediones (TZD) are ligands known to bind to and activate the nuclear peroxisome proliferator-activated receptor γ (PPARγ), and are currently used as insulin sensitizers in type 2 diabetes. Recently, several studies have shown that TZD may have a role in renal protection in various experimental models. However, the precise mechanisms by which TZD may possibly affect tubular cell survival after injury remain unclear. We studied the influence of the TZD rosiglitazone on PPARγ expression and cell function with cellular damage induced by increasing hydrogen peroxide (H₂O₂) concentrations in bovine renal tubular epithelial cells (bEPC) to determine whether rosiglitazone is cytoprotective under these conditions. Methods: bEPC were cultured in the presence of H₂O₂ after pretreatment with or without 25 µM rosiglitazone. The expression of PPARγ mRNA and protein were determined using RT-PCR or Western blots, respectively, after 6 and 24 h. Some cells also received actinomycin D or cycloheximide and PPARγ protein expression was tested. Proliferation rates of cultures were compared after 15 h and after a recovery phase of 6 days. Apoptosis was assessed by DNA fragmentation. Nuclear PPARγ activity was evaluated by electrophoretic mobility shift assay (EMSA), and the cellular location was detected using immunofluorescence. Results: Incubation of bEPC with H₂O₂ concentrations up to 0.75 mM did not induce apoptosis as tested by DNA fragmentation assay, but significantly and dose-dependently reduced proliferation 15 h after injury as measured by [³H]thymidine incorporation. 25 µM rosiglitazone alone also reduced proliferation and failed to attenuate the H₂O₂-mediated inhibition of proliferation. However, rosiglitazone facilitates recovery of tubular cells 6 days after H₂O₂-induced injury. Rosiglitazone (25 µM) increased PPARγ mRNA and protein expression in bEPC in the absence of H₂O₂. Rosiglitazone failed to increase PPARγ mRNA in cells with oxidative stress, but Western blots revealed an increase in cellular PPARγ protein content in the presence of rosiglitazone and increasing concentrations of H₂O₂. This increase in PPARγ protein content was almost totally abolished in the presence of 1 µg/ml cycloheximide, but was only marginally reduced by 0.1 µg/ml actinomycin D. EMSA showed a robust increase in nuclear PPARγ protein binding in vitro to its consensus site after rosiglitazone whereas H₂O₂ treatment reduced PPARγ activation. Rosiglitazone treatment of cells with oxidative stress preserved nuclear transactivation of PPARγ. Conclusions: Rosiglitazone increases the PPARγ content in bEPC after H₂O₂-induced injury by a posttranscriptional mechanism. Activation of PPARγ facilitates the long-term recovery of tubular cells 6 days after oxidative injury, but had no effect on the attenuated proliferation s...

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“…Bovine and porcine EDC were prepared as previously described [Sommer et al, 2002]. In brief, the lumen of pulmonary arteries was fi lled with 0.2-1.0 mg/ml collagenase (Worthington, Freehold, N.J., USA; 216 IU/ml; 0.6 mg/ml) in phosphate-buffered saline and Sommer/Gerth/Stein/Wolf Cells Tissues Organs 2005;180:204-214 206 incubated at 37 ° C for 12 min.…”

Section: Pulmonary Arterial Endothelial Cellsmentioning

confidence: 99%

Transdifferentiation of Endothelial and Renal Tubular Epithelial Cells into Myofibroblast-Like Cells under in vitro Conditions: A Morphological Analysis

Sommer¹,

Gerth²,

Stein³

et al. 2005

Cells Tissues Organs

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Renal fibrosis is a hallmark of progressive kidney disease and is characterized by an accumulation of extracellular-matrix-synthesizing cells in the glomerulus and tubulointerstitium. This population of myofibroblast-like cells (MFLC) is heterogeneous. It has been experimentally shown, for example, that tubular epithelial cells could change their phenotype into MFLC under certain circumstances, a process called epithelial-mesenchymal transdifferentiation. However, MFLC may also originate from other sources. Therefore, we examined whether endothelial cells (EDC) are able to transdifferentiate into MFLC in vitro. We compared potential differences between syngeneic tubular epithelial cells (EPC) and EDC during transdifferentiation into MFLC using bovine and porcine EDC isolated from pulmonary arteries, and glomerular capillaries. Renal tubular EPC were prepared from bovine renal cortical tissue by collagenase digestion and isolation from homogeneous cell monolayers. Bovine renal tubular EPC stained positive for cytokeratin. Furthermore, tubular EPC selectively incoporated labeled bovine serum albumin, a typical property of differentiated renal tubular cells. EDC were characterized by the absence of epithelial markers (e.g. cytokeratin), but stained positive for vWF. The transdifferentiation of EDC into MFLC occurs sequentially in two steps: First, by a rapid reversible transformation in postconfluent or clonal cultures without the need of cytokine stimulation and second, by a prolonged secondary step in the presence of the transformation-accelerating cytokines and the absence of adherently growing EDC. Thus, EDC that are able to sprout can also irreversibly transdifferentiate into MFLC. On the other hand, prolonged incubation of EPC in the presence of cytokines such as transforming growth factor-β1 and tumor necrosis factor-α leads only to a very small number of MFLC without the ability to further proliferate. Our in vitro data suggest that EDC can more easily transdifferentiate into MFLC than syngeneic renal tubular EPC.

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Interleukin 4 Co-Stimulates the PDGF-BB- and bFGF-Mediated Proliferation of Mesangial Cells and Myofibroblasts

Cited by 14 publications

References 32 publications

CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

Rosiglitazone Increases PPARγ in Renal Tubular Epithelial Cells and Protects against Damage by Hydrogen Peroxide

Transdifferentiation of Endothelial and Renal Tubular Epithelial Cells into Myofibroblast-Like Cells under in vitro Conditions: A Morphological Analysis

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