A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis

Wei, Chi-Chen; Chang, Ming-Shi

doi:10.1038/gene.2008.61

Cited by 11 publications

(15 citation statements)

References 48 publications

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“…Although not all mIL-20R1a transgenic mice developed renal calcium deposition, these mice could still serve as a useful model for studies not only on kidney stones but also on lupus nephritis. 23 We found other pathological changes in procreation and hematopoiesis in these transgenic mice (data not shown). Further studies are necessary to clarify whether mIL-20R1a is involved in the pathophysiological events that underlie procreation-or hematopoiesis-related diseases.…”

Section: Discussionmentioning

confidence: 71%

“…Furthermore, elevated mIL-20R1a in splenocytes of SLE-prone mice promoted stimulated splenic B cells to produce more IL-10. 23 The in vitro study showed the possible biological roles of mIL-20R1a in lupus nephritis. 23 Besides exploring the involvement of mIL-20R1a in the pathogenesis of lupus nephritis, we also sought to investigate the in vivo function of mIL-20R1a.…”

Section: Introductionmentioning

confidence: 99%

“…23 The in vitro study showed the possible biological roles of mIL-20R1a in lupus nephritis. 23 Besides exploring the involvement of mIL-20R1a in the pathogenesis of lupus nephritis, we also sought to investigate the in vivo function of mIL-20R1a. Generation of transgenic mice and knockout mice are two common strategies used to study the in vivo function of a novel gene.…”

Section: Introductionmentioning

confidence: 99%

“…However, no significant interaction between mIL-20R1a and mIL-19 or mIL-20 was detected. 23 This soluble protein can act on mesangial cells directly and result in phosphorylation of AKT and C-Jun N-terminal kinase (JNK). In addition, mIL-20R1a may stimulate the production of chemoattractants, renal fibrogenic factors and reactive oxygen species (ROS) by mesangial cells.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, mIL-20R1a may stimulate the production of chemoattractants, renal fibrogenic factors and reactive oxygen species (ROS) by mesangial cells. 23 These mIL-20R1a-mediated effects on mesangial cells could be amplified through increased transcription of mIL-20R1a by angiotensin II, platelet-derived growth factors and lipopolysaccharide (LPS), important mediators involved in the pathogenesis of lupus nephritis. Furthermore, elevated mIL-20R1a in splenocytes of SLE-prone mice promoted stimulated splenic B cells to produce more IL-10.…”

Section: Introductionmentioning

confidence: 99%

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Mouse interleukin-20 receptor 1a targets renal epithelial cells and is associated with renal calcium deposition

Wei

Chang

2008

Genes Immun

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We previously identified a novel transcript, mouse (m)IL-20R1a, generated by alternative splicing of the mIL-20R1 gene and studied its possible in vitro functions. However, the function of mIL-20R1a in vivo is unknown. Overexpression of mIL-20R1a in transgenic FvB/N mice resulted in the pathological change of excess calcium deposited in the kidneys. The interplay between renal epithelial cells and calcium oxalate (CaOx) was important in the crystallization involved in the formation of renal stones (nephrolithiasis). Thus, we investigated and compared the responses of mouse renal proximal (TKPTS) and collecting (M-1) tubule cell lines to CaOx with or without mIL-20R1a. The renal epithelial cell lines exposed to CaOx in the presence of mIL20R1a showed significantly increased lactate dehydrogenase release; loss of cell viability through apoptosis; increased CaOx internalization; higher tumor necrosis factor (TNF)-a, MCP-1 and RANTES expression; and higher reactive oxygen species production. Interleukin-6, TNF-a and MCP-1 were also upregulated in the kidneys of mIL-20R1a transgenic mice. These effects of mIL-20R1a on CaOx-exposed renal epithelial cells showed that mIL-20R1a functioned as an aggravating factor in promoting calcium deposition in kidney of mice.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mouse interleukin-20 receptor 1a targets renal epithelial cells and is associated with renal calcium deposition

Wei

Chang

2008

Genes Immun

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Decreased Interleukin‐20 Expression in Scleroderma Skin Contributes to Cutaneous Fibrosis

Kudo

Jinnin

Asano

et al. 2014

Arthritis & Rheumatology

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Objective To clarify the role of interleukin-20 (IL-20) in the regulatory mechanism of extracellular matrix expression and to determine the contribution of IL-20 to the phenotype of systemic sclerosis (SSc). Methods Protein and messenger RNA (mRNA) levels of collagen, Fli-1, IL-20, and IL-20 receptor (IL-20R) were analyzed using polymerase chain reaction (PCR) array, immunoblotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time PCR. Results PCR array revealed that IL-20 decreased gene expression of α2(I) collagen (0.03-fold), Smad3 (0.02-fold), and endoglin (0.05-fold) in cultured normal dermal fibroblasts. Fli-1 protein expression was induced by IL-20 (~2-fold). The inhibition of collagen by IL-20, the induction of Fli-1 by IL-20, and the reduction of Smad3 and endoglin by IL-20 were also observed in SSc fibroblasts. Serum IL-20 levels were reduced only slightly in SSc patients but were significantly decreased in patients with scleroderma spectrum disorders (the prodromal stage of SSc) compared with those in normal subjects (111.3 pg/ml versus 180.4 pg/ml; P < 0.05). On the other hand, IL-20 mRNA expression in SSc skin was decreased compared with that in normal skin (P < 0.05), which may result in the induction of collagen synthesis in SSc dermal fibroblasts. IL-20R was expressed in normal and SSc fibroblasts. Moreover, IL-20 supplementation by injection into the skin reversed skin fibrosis induced by bleomycin in mice (~0.5-fold). Conclusion IL-20 reduces basal collagen transcription via Fli-1 induction, while down-regulation of Smad3 and endoglin may cancel the effect of transforming growth factor β in SSc fibroblasts. To confirm the therapeutic value of IL-20 and IL-20R, their function and expression in vivo should be further studied.

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Astrocytes produce IL-19 in response to bacterial challenge and are sensitive to the immunosuppressive effects of this IL-10 family member

Cooley

Chauhan

Donneyz

et al. 2014

Glia

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There is growing appreciation that resident glial cells can initiate and/or regulate inflammation following trauma or infection in the central nervous system (CNS). We have previously demonstrated the ability of microglia and astrocytes to respond to bacterial pathogens or their products by rapid production of inflammatory mediators, followed by the production of the immunosuppressive cytokine interleukin (IL)210. IL-19, another member of the IL-10 family of cytokines, has been studied in the context of a number of inflammatory conditions in the periphery and is known to modulate immune cell activity. In the present study, we demonstrate the constitutive and/or inducible expression of IL-19 and its cognate receptor subunits, IL-19Rα and IL-19Rβ (also known as IL-20R1 and IL-20R2, and IL-20RA and IL-20RB), in mouse brain tissue, and by primary murine and human astrocytes. We also provide evidence for the presence of a novel truncated IL-19Rα transcript variant in mouse brain tissue, but not glial cells, that shows reduced expression following bacterial infection. Importantly, IL-19R functionality in GLIA is indicated by the ability of IL-19 to regulate signaling component expression in these cells. Furthermore, while IL-19 itself had no effect on glial cytokine production, IL-19 treatment of bacterially infected or Toll-like receptor ligand stimulated astrocytes significantly attenuated pro-inflammatory cytokine production. The bacterially induced production of IL-19 by these resident CNS cells, the constitutive expression of its cognate receptor subunits, and the immunomodulatory effects of this cytokine, suggest a novel mechanism by which astrocytes can regulate CNS inflammation.

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A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis

Cited by 11 publications

References 48 publications

Mouse interleukin-20 receptor 1a targets renal epithelial cells and is associated with renal calcium deposition

Mouse interleukin-20 receptor 1a targets renal epithelial cells and is associated with renal calcium deposition

Decreased Interleukin‐20 Expression in Scleroderma Skin Contributes to Cutaneous Fibrosis

Astrocytes produce IL-19 in response to bacterial challenge and are sensitive to the immunosuppressive effects of this IL-10 family member

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