Interleukin‐6 and Interleukin‐6 Receptor are Expressed by Cultured Glomerular Epithelial Cells

Moutabarrik, A; Nakanishi, I; Ishibashi, M

doi:10.1111/j.1365-3083.1994.tb03448.x

Cited by 25 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous investigators have suggested that IL-6 and TNF are produced by human GEC [26, 27, 28]. The current study confirms these observations and provides the new observation that IL-1 is also made by this cell type.…”

Section: Discussionsupporting

confidence: 81%

“…To determine if Stx-1-stimulated GEC cytokine production might be modulated by LPS, which is likely present in the serum of patients with HUS, the effect of LPS alone or in combination with Stx-1 was evaluated. LPS alone increased IL-6 and TNF, but not IL-1, production by GEC (while LPS stimulation of IL-6 production by GEC has been described [26], to our knowledge, this is the first report of LPS stimulation of TNF release by this cell type). Notably, LPS stimulation of IL-6 and TNF release occurred in the absence of any apparent cytotoxicity or inhibition of protein synthesis.…”

Section: Discussionmentioning

confidence: 89%

See 1 more Smart Citation

Shiga Toxin-1 Regulation of Cytokine Production by Human Glomerular Epithelial Cells

Hughes

Stricklett

Kohan

2001

Nephron

View full text Add to dashboard Cite

Background/Aims: Inflammatory cytokines may enhance renal injury in post-diarrheal hemolytic uremic syndrome (Stx HUS) by enhancing the cytotoxic effect of Shiga toxins (Stx). The sources of inflammatory cytokines in Stx HUS are unclear. Since Stx-1 potently inhibits protein synthesis by glomerular epithelial cells (GEC) and increases cytokine release by renal epithelial cells, we examined Stx-1 regulation of cytokine production by human GEC. Methods: Stx-1 (and cycloheximide (CHX), another protein synthesis inhibitor) cytotoxicity, protein synthesis inhibition, and effect on interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) release and mRNA levels were determined. Results: Stx-1 alone had a modest stimulatory effect on inflammatory cytokine production by GEC that occurred at toxin concentrations ranging from minimal to 50% inhibition of protein synthesis. CHX, at concentrations that produced similar inhibition of protein synthesis, increased IL-1, IL-6, and TNF protein release and mRNA accumulation, but in a different time- and dose-dependent pattern than Stx. Lipopolysaccharide (LPS) did not change IL-1, but stimulated IL-6 and TNF production. LPS and Stx-1 combined stimulated production of all three cytokines to a greater extent than either toxin alone. Conclusion: These data indicate that: (1) Stx-1 alone modestly stimulates GEC inflammatory cytokine production; (2) LPS and Stx-1 combined can potently enhance GEC cytokine release, and (3) this action of Stx-1 may relate in part to inhibition of protein synthesis but cannot be fully attributed to this effect.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 89%

Shiga Toxin-1 Regulation of Cytokine Production by Human Glomerular Epithelial Cells

Hughes

Stricklett

Kohan

2001

Nephron

View full text Add to dashboard Cite

show abstract

“…We hypothesize that higher urine sIL-6R might originate from the local production of sIL-6R in epithelial cells of the transplant. Activated epithelial cells can most likely secrete sIL-6R, as suggested by culture experiments in which stimulation of glomerular epithelial cells by proinflammatory mediators, such as lipopolysaccharide, increased the expression of IL-6R mRNA (25).…”

Section: Sil-6r Urine Levels In Patients and Healthy Controlsmentioning

confidence: 97%

“…IL-6 is a 26-kDa glycoprotein that is produced by many cell types, such as T and B lymphocytes, fibroblasts, macrophages, and endothelial and epithelial cells (23)(24)(25). IL-6 induces the expression of sIL-6R, a 50-kDa protein that is secreted by human cell lines derived from peripheral blood mononuclear cells, glomerular epithelial cells, osteoblasts, and cells of the central nervous system (24,25). sIL-6R was shown to bind IL-6, thereby prolonging the plasma half life of IL-6 (26).…”

Section: Sil-6r Urine Levels In Patients and Healthy Controlsmentioning

confidence: 99%

High urine sIL-6R as a predictor of late graft failure in renal transplant recipients

Sadeghi

Daniel²,

Wiesel³

et al. 2003

Transplantation

View full text Add to dashboard Cite

show abstract

“…IL-6 is secreted by different cells, including podocytes, and is a vital modulator of immune and inflammatory responses (31–35). IL-6 has been shown to act in a proinflammatory as well as anti-inflammatory manner, and it is thought to act as an immunological switch (36).…”

Section: Introductionmentioning

confidence: 99%

Podocytes Regulate Neutrophil Recruitment by Glomerular Endothelial Cells via IL-6–Mediated Crosstalk

Kuravi

McGettrick

Satchell

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

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-α 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-α (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.

show abstract

Interleukin‐6 and Interleukin‐6 Receptor are Expressed by Cultured Glomerular Epithelial Cells

Cited by 25 publications

References 26 publications

Shiga Toxin-1 Regulation of Cytokine Production by Human Glomerular Epithelial Cells

Shiga Toxin-1 Regulation of Cytokine Production by Human Glomerular Epithelial Cells

High urine sIL-6R as a predictor of late graft failure in renal transplant recipients

Podocytes Regulate Neutrophil Recruitment by Glomerular Endothelial Cells via IL-6–Mediated Crosstalk

Contact Info

Product

Resources

About