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INTERLEUKIN 20
LATEST LITERATURE
1: Arthritis and rheumatism, 2010 Aug 18,
Interleukin-20 antibody is a potential therapeutic for experimental arthritis.
[Abstract]OBJECTIVE:: Interleukin (IL)-20 is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). We investigated whether anti-IL-20 antibody treatment would modulate the severity of the disease in a collagen-induced arthritis (CIA) rat model. METHODS:: We generated a CIA model by immunizing rats with bovine type II collagen. CIA rats were subcutaneously treated with anti-IL-20 antibody 7E, TNF blocker (etanercept), or 7E combined with etanercept. Arthritis severity was determined by hind-paw thickness, severity score, cartilage damage, bone mineral density, cytokine production, which were evaluated using radiological scans, micro-computed tomography and ELISA. To analyze gene regulation by IL-20, rat synovial fibroblasts (SFs) were isolated and analyzed for the expression of receptor activator for nuclear factor-kappaB ligand (RANKL), IL-17, and TNF-alpha. We also used real-time qPCR and flow cytometry to determine IL-20 regulated RANKL in mouse osteoblastic MC3T3-E1 and Th17 cells. RESULTS:: In vivo, 7E alone or combined with etanercept significantly reduced the severity of arthritis by decreasing hind-paw thickness and swelling; prevented cartilage damage and bone loss; and reduced the expression of IL-20, IL-1beta, IL-6, RANKL and matrix metalloproteinase enzymes (MMPs) in synovial tissue. In vitro, IL-20 induced TNF-alpha expression in CIA SFs. IL-20 markedly induced RANKL production in CIA SFs, osteoblasts, and Th17 cells. CONCLUSION:: Selectively blocking IL-20 inhibited inflammation and bone loss in CIA rats. 7E combined with etanercept protected CIA rats better than etanercept alone. Our findings provide evidence that IL-20 is a novel target, and that 7E may be a potential therapeutic for RA.
2: European journal of immunology, 2009 Oct 14,
The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: A novel immunological cascade with potential relevance in psoriasis.
[Abstract]Psoriasis is a common chronic skin disease. Recent studies demonstrated that IL-20 and IL-22, cytokines produced by keratinocytes and T-cells, respectively, both inhibit keratinocyte terminal differentiation and induce psoriasis-like epidermis alterations. Here, we investigated the relationship between these mediators. Whereas IL-20 was not able to regulate IL-22 production, IL-22 induced IL-20 mRNA and protein in human keratinocytes. However, IL-22 had only a minimal effect, if any, on IL-19 and IL-26. Cutaneous IL-20 was also elevated in mice following IL-22 application. Accordingly, some of the IL-22 effects on differentiation regulating genes were partially mediated by an endogenous, secreted protein and attenuated by anti-IL-20 antibodies. Like IL-22, IL-17A and TNF-alpha induced IL-20 in keratinocytes, whereas IFN-gamma and IL-20 itself did not. Furthermore, IL-17A and TNF-alpha individually strengthened the IL-22-induced IL-20 production. In lesional skin of psoriasis patients, highly elevated IL-20 levels strongly correlated with IL-22, and to a lesser extent, with IL-17A and TNF-alpha. As previously shown for IL-22, IL-20 blood levels correlated with the disease severity, although with a lower significance. This study demonstrates that a T-cell mediator induces a tissue cell mediator with similar effects to its own and therefore suggests the existence of a novel type of pathogenetic cascade.
3: Developmental and comparative immunology, 2009 Sep 23, 39(10)
Cloning of a novel interleukin (IL)-20-like gene in rainbow trout Oncorhynchus mykiss gives an insight into the evolution of the IL-10 family.
[Abstract]A novel IL-20-like (IL-20L) gene has been analyzed in rainbow trout. It has a six exon/five intron gene organisation and is translated into 181 amino acids (aa) with a signal peptide of 25aa and a mature peptide of 156aa. The trout IL-20L translation shares highest identities to other IL-20L molecules from fish and to IL-20 in mammals. Phylogenetic analysis showed that the fish IL-20L molecules form an independent clade but cluster with the group containing the IL-19, IL-20 and IL-24 molecules from higher vertebrates with a high bootstrap value (89%). The fish IL-20L genes are syntenically in the same location as mammalian IL-19/IL-20/IL-24. Gene organisation and multiple alignment also showed a close relationship of fish IL-20L genes to the mammalian IL-19/IL-20/IL-24 subfamily. These data suggest that the fish IL-20L molecules may have arisen from an ancestral gene that gave rise to IL-19, IL-20 and IL-24 in higher vertebrates. A high level of IL-20L expression in immune related tissues and in the brain, suggests an important role of the fish IL-20L molecule in both the fish immune system and nervous system. Although the exact cell types expressing IL-20L have yet to be defined, macrophages express IL-20L. Moreover, the IL-20L expression in the macrophage cell line RTS-11 was modulated by pro-inflammatory cytokines, signalling pathway activators, microbial mimics and the immuno-suppressor dexamethasone. These data suggest that trout IL-20L is an important player in the cytokine network. The increased expression of IL-20L was only detected at late stages (4-24h) of LPS stimulation in RTS-11 cells and in spleen 24-72h after infection with Yersinia ruckeri, and suggests that the increased expression of IL-20L by LPS and infection may be via the rapid increase of pro-inflammatory cytokines (e.g., IL-1beta) and other factors that is known to occur.
4: European journal of immunology, 2009 Oct, 39(10)
IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression.
[Abstract]IL-20 cytokine subfamily members, including IL-19, IL-20, and IL-24, are highly expressed in psoriatic skin lesions. Here, we demonstrate that psoriasis mediators IL-17 and IL-22 synergistically induce the production of IL-20 subfamily proteins in cultured human keratinocytes. Interestingly, expression of the IL-22 receptor (IL-22R) also increased in epidermal lesions versus normal skin. IL-22R over-expression using an adenoviral vector to mimic psoriatic conditions in cultured keratinocytes significantly enhanced IL-17- and IL-22-induced production of IL-20 subfamily cytokines. Furthermore, IL-17 and IL-22 coordinately enhanced MIP-3alpha, IL-8, and heparin-binding EGF-like growth factor (HB-EGF) production, depending on the amount of IL-22R expression. Additionally, because IL-20 and IL-24 share the IL-22R with IL-22, the function of IL-20 and IL-24 was also increased. IL-20 and IL-24 have effects similar to that of IL-22; IL-24 showed more potent expression than IL-20. A combination of IL-24 and IL-17 increased the production of MIP-3alpha, IL-8, and HB-EGF, as did a combination of IL-22 and IL-17. These data indicate that increased IL-22R expression in epidermal keratinocytes contributes to the pathogenesis of psoriasis through enhancing the coordinated effects of IL-22 and IL-17, inducing the production of the IL-20 subfamily, chemokines, and growth factors.
5: Nutrition, metabolism, and cardiovascular diseases : NMCD, 2009 May 27, 78(1)
Interleukin-20 circulating levels in obese women: Effect of weight loss.
[Abstract]BACKGROUND AND AIMS: Obesity is associated with an increased risk of developing atherosclerosis. Interleukin-20 (IL-20) is a pleiotropic cytokine thought to be involved in the onset and progression of atherosclerosis. The aim of this study was to determine whether circulating levels of IL-20 are elevated in obese women and whether they could be affected by a substantial decrease in body weight. METHODS AND RESULTS: Fifty obese and 50 age-matched, normal weight, premenopausal women participated in the study. Obese women entered into a medically supervised weight loss program aimed at reducing body weight to 90% of baseline. We measured anthropometric, glucose and lipid parameters, and IL-20, C-Reactive Protein (CRP) and interleukin-10 (IL-10) circulating levels. Circulating IL-20 and CRP levels were significantly higher in obese than control women (P=0.01), while IL-10 levels were significantly lower; IL-20 levels were positively associated with body weight (r=0.35; P=0.02) and visceral fat (waist-hip ratio; r=0.32; P=0.025). Caloric restriction-induced weight loss (>10% of original weight) over 6 months reduced IL-20 levels from 152 (112/184) to 134 (125/153)pg/ml (median and 25%/75%; P=0.03), and it was positively associated with changes in body mass index and waist-hip ratio. CONCLUSION: In premenopausal obese women, IL-20 levels are higher than matched normal weight control women, are associated with body weight and waist-hip ratio, and are reduced by weight loss.
6: Journal of immunology (Baltimore, Md. : 1950), 2009 Apr 15, 182(8)
IL-20 is regulated by hypoxia-inducible factor and up-regulated after experimental ischemic stroke.
[Abstract]IL-20, an IL-10 family member, is involved in various inflammatory diseases, such as psoriasis, rheumatoid arthritis, and atherosclerosis. We investigated whether hypoxia in vitro and an in vivo model of ischemic stroke would up-regulate IL-20 expression. In vitro, IL-20 expression increased in hypoxic HaCaT, HEK293 cells, chondrocytes, monocytes, and glioblastoma cells. Inhibition of hypoxia-inducible factor 1alpha inhibited CoCl(2)-induced IL-20 expression. We identified two putative hypoxia response elements in the human il20 gene promoter. Promoter activity assays showed that CoCl(2) mimicked hypoxia-activated luciferase reporter gene expression. In vivo, experimental ischemic stroke up-regulated IL-20 in the sera and brain tissue of rats. IL-20 stained positively in glia-like cells in peri-infarcted lesions, but not in contralateral tissue. Administration of IL-20 mAb ameliorated ischemia-induced brain infarction of rats after experimental ischemic stroke. In vitro, RT-PCR analysis showed that glioblastoma cells, GBM8901, expressed IL-20 and its receptor subunits IL-20R1, IL-20R2, and IL-22R1. IL-20 induced cell proliferation in GBM8901 cells by activating the JAK2/STAT3 and ERK1/2 pathways. IL-20 also induced production of IL-1beta, IL-8, and MCP-1 in GBM8901 cells. We conclude that IL-20 was responsive to hypoxia in vitro and in the ischemic stroke model and that up-regulation of IL-20 in the ischemic brain may contribute to brain injury.
7: Journal of molecular medicine (Berlin, Germany), 2009 May, 87(5)
IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not.
[Abstract]Psoriasis is a common chronic skin disease with a largely unknown pathogenesis. We demonstrate here that transgenic over-expression of interleukin (IL)-22 in mice resulted in neonatal mortality and psoriasis-like skin alterations including acanthosis and hypogranularity. This cutaneous phenotype may be caused by the direct influence of IL-22 on keratinocytes, since this cytokine did not affect skin fibroblasts, endothelial cells, melanocytes, or adipocytes. The comparison of cytokines with hypothesized roles in psoriasis pathogenesis determined that neither interferon (IFN)-gamma nor IL-17, but only IL-22 and, with lower potency, IL-20 caused psoriasis-like morphological changes in a three-dimensional human epidermis model. These changes were associated with inhibited keratinocyte terminal differentiation and with STAT3 upregulation. The IL-22 effect on differentiation-regulating genes was STAT3-dependent. In contrast to IL-22 and IL-20, IFN-gamma and IL-17 strongly induced T-cell and neutrophilic granulocyte-attracting chemokines, respectively. Tumor necrosis factor-alpha potently induced diverse chemokines and additionally enhanced the expression of IL-22 receptor pathway elements and amplified some IL-22 effects. This study suggests that different cytokines are players in the psoriasis pathogenesis although only the IL-10 family members IL-22 and IL-20 directly cause the characteristic epidermal alterations.
8: Microvascular research, 2009 Jun, 78(1)
IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation.
[Abstract]IL-20 is an arteriogenic cytokine that remodels collateral networks in vivo, and plays a role in cellular organization. Here, we investigate its role in lymphangiogenesis using a lymphatic endothelial cell line, hTERT-HDLEC, which expresses the lymphatic markers LYVE-1 and podoplanin. Upon stimulation of hTERT-HDLEC with IL-20, we found an increase in the intracellular free calcium concentration, in Akt and eNOS phosphorylations as well as in perinuclear NO production. We found that eNOS phosphorylation and NO synthesis are highly dependent on the PI3K/Akt signalling pathway. We also found an IL-20 induced phosphorylation of Erk1/2 and mTOR, and using the MEK inhibitor PD98059 and mTOR complex inhibitor rapamycin we demonstrated the importance of these signalling pathways in IL-20-mediated proliferation. IL-20 triggered actin polymerization and morphological changes resulting in elongated cell structures, and in matrigels, IL-20 caused tube formations of hTERT-HDLEC in a PI3K- and mTOR dependent way. In a sprouting assay we found that IL-20 caused cell migration within 24 h at a rate comparable to VEGF-C, and this migration could be inhibited by wortmannin and rapamycin. These data show that IL-20 activates cell signalling resulting in lymphangiogenic processes including migration, proliferation and tube formation. Thus, IL-20 is a cytokine that has the potential of activating or modulating the formation of lymphatic vessels.
9: Journal of immunology (Baltimore, Md. : 1950), 2009 Jan 15, 182(2)
IL-20 receptor 2 signaling down-regulates antigen-specific T cell responses.
[Abstract]The recently described cytokines IL-19, IL-20, and IL-24 share structural homology with IL-10 and are therefore classified as members of the IL-10 family of cytokines. Although it has long been speculated that signaling by their heterodimeric receptor complexes (IL-20R1/IL-20R2 and IL-22R/IL-20R2) influences immunological processes, the target cells for this group of cytokines are still unclear. By generating a knockout mouse strain deficient for the common IL-20R beta-chain (IL-20R2), we show that IFN-gamma and IL-2 secretion is significantly elevated after stimulation of IL-20R2-/--deficient CD8 and CD4 T cells with Con A or anti-CD3/CD28 in vitro. IL-10 secretion by activated IL-20R2-/- CD4 cells was diminished. Consistent with our in vitro results, significantly more Ag-specific CD8 IFN-gamma+ and CD4 IFN-gamma+ T cells developed to locally applied DNA vaccines in IL-20R2-deficient mice. In a T cell-dependent model of contact hypersensitivity, IL-20R2 knockout mice were more sensitive to the contact allergen trinitro-chloro-benzene. Thus, IL-20R2 signaling directly regulates CD8 and CD4 T cell answers in vitro and in vivo. For the first time, we provide evidence that IL-19, IL-20, and IL-24 are part of a signaling network that normally down-modulates T cell responses in mice.
10: Genes and immunity, 2008 Dec 11, 182(2)
Mouse interleukin-20 receptor 1a targets renal epithelial cells and is associated with renal calcium deposition.
[Abstract]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 mIL-20R1a showed significantly increased lactate dehydrogenase release; loss of cell viability through apoptosis; increased CaOx internalization; higher tumor necrosis factor (TNF)-alpha, MCP-1 and RANTES expression; and higher reactive oxygen species production. Interleukin-6, TNF-alpha 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.Genes and Immunity advance online publication, 11 December 2008; doi:10.1038/gene.2008.93.
11: The British journal of dermatology, 2009 Feb, 160(2)
Interleukin-20 plays a critical role in maintenance and development of psoriasis in the human xenograft transplantation model.
[Abstract]BACKGROUND: Interleukin (IL)-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interestingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the aetiology of psoriasis is unknown. OBJECTIVES: In this study, we investigate the effects both of blocking IL-20 signalling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin. METHODS: We employed the human skin xenograft transplantation model in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immuno-deficient mice. The transplanted mice were treated with anti-IL-20 antibodies or recombinant human IL-20. RESULTS: We demonstrate that blocking IL-20 signalling with anti-IL-20 antibodies induces psoriasis resolution and inhibits psoriasis induction. We also demonstrate that continuous IL-20 infusion, together with injection of additional nonactivated leucocytes, promotes induction of psoriasis in nonlesional skin from patients with psoriasis. CONCLUSIONS: The results suggest that IL-20 plays a critical role in the induction and maintenance of psoriasis, and IL-20 is suggested as a new possible specific target in psoriasis treatment.
12: Clinical immunology (Orlando, Fla.), 2008 Nov, 129(2)
Interleukin-20 targets renal mesangial cells and is associated with lupus nephritis.
[Abstract]Lupus nephritis is one manifestation of systemic lupus erythematosus (SLE). Interleukin (IL)-10 is involved in the pathogenesis of SLE. To determine whether IL-20, a member of the IL-10 family, is associated with lupus nephritis, we analyzed the expression of IL-20 and its receptors in mesangial cells derived from SLE-prone, NZB/W, and DBA/W mice. IL-20 and its receptors were upregulated in mesangial cells from NZB/W mice. Incubating IL-20 with mesangial cells upregulated the transcripts of CCL2 (MCP-1), CCL5 (RANTES), CXCL10 (IP-10), IL-6, iNOS, and ROS, all of which are involved in the pathogenesis of lupus nephritis. IL-20 specifically activated the downstream signal ERK 1/2. We also detected human IL-20 protein in both mesangial cells and inflammatory cells in kidney biopsies of patients with lupus nephritis. Our results reveal the novel effects of IL-20 on mesangial cells and its association with lupus nephritis.
13: Genes and immunity, 2008 Dec, 9(8)
A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis.
[Abstract]We identified a novel soluble protein, mouse (m)IL-20R1a, generated by alternative splicing of the mIL-20R1 gene, which encodes one subunit of the receptor complex for mIL-19, mIL-20 and mIL-24. mIL-20R1a has 77.14% amino-acid identity with the extracellular domain of mIL-20R1. However, no significant interaction between mIL-20R1a and mIL-19 or mIL-20 was detected. Consequently, we aimed to clarify whether mIL-20R1a might function as a novel effector on certain cells. Competitive binding assays demonstrated that mIL-20R1a bound to cell surfaces and resulted in AKT and JNK phosphorylation in primary mesangial cells (MCs) isolated from either the wild-type mice, DBA/W mice, or the SLE-prone mice, NZB/W mice. NZB/W MCs expressed more mIL-20R1a transcript than DBA/W MCs did. Furthermore, mIL-20R1a-treated NZB/W MCs produced higher level of chemokines, renal fibrogenic factors and ROS than mIL-20R1a-treated DBA/W MCs did. These factors are involved in the pathogenesis of lupus nephritis. Endogenous mIL-20R1a was upregulated in the bladder, colon and spleen tissue of NZB/W mice. Elevated mIL-20R1a in the spleen tissue of NZB/W mice was expressed mainly in monocytes and B cells. mIL-20R1a further induced mIL-10 production by the anti-IgM antibody-stimulated B cells in NZB/W mice. Therefore, mIL-20R1a-mediated effects may exacerbate the disease outcome of lupus nephritis.
14: Ugeskrift for laeger, 2008 Sep 1, 170(36)
[Interleukin-20--a new target in psoriasis treatment]
[Abstract]Interleukin-20 (IL-20) is suggested as a new target in psoriasis treatment. It was first described in 2001, and the potential role of this cytokine in psoriasis was suggested because mice which were over-expressing IL-20 developed a psoriasis-like phenotype of the skin. Subsequently, IL-20 expression levels were found to be increased in psoriasis skin, and it was observed that these levels normalized upon psoriasis treatment. In the psoriasis xenograft transplantation model, administration of IL-20 to non-lesional psoriasis skin transplanted onto immune-deficient mice demonstrated that IL-20 was involved in the psoriasis induction. More interestingly, improvement of psoriasis was induced by blocking IL-20 signaling.
15: Spine, 2008 Sep 1, 33(19)
IL-20 may contribute to the pathogenesis of human intervertebral disc herniation.
[Abstract]STUDY DESIGN: The gene expression of interleukin (IL)-20 on human herniated intervertebral disc. OBJECTIVE.: To elucidate the role of novel cytokine IL-20 in the pathogenesis of human intervertebral disc (IVD) herniation. SUMMARY OF BACKGROUND DATA: IL-20 is involved in inflammatory diseases such as psoriasis, atherosclerosis, and rheumatoid arthritis, etc. However, IL-20 is never reported to be associated with the pathogenesis of human disc herniation. METHODS: Twenty consecutive patients who were diagnosed with IVD herniation and received open discectomy were included in this study. The retrieved disc material specimens and the isolated primarily cultured disc cells were immunohistochemically stained to detect the expression of IL-20 and its receptor subunits (IL-20R1, IL-20R2, and IL-22R1). Besides, to investigate the in vitro response of IL-20 on human herniated intervertebral disc, we analyzed the effects of IL-20 alone, in combination with IL-1beta, and IL-1beta alone on the gene expression and protein levels of various cytokines, chemokines, matrix metalloproteinases (MMPs), etc. RESULTS: IL-20 and its receptors were detectable in human herniated disc tissues and isolated disc cells. In vitro, IL-1beta induced the expression of IL-20. Furthermore, IL-20 induced transcripts of IL-1beta, IL-6, vascular endothelial growth factor (VEGF), MMP-3, and monocyte chemoattractant protein (MCP-1) on primarily cultured human disc cells. IL-1beta induced transcripts of IL-1beta, IL-6, IL-8, VEGF, MMP3, and MCP-1. IL-20 combined with IL-1beta induced transcripts of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-8, MMP-3, and MCP-1 to a level higher than those found in cells treated with IL-20 or IL-1beta alone.Enzyme-linked immunosorbent assay, analysis also showed that IL-20 combined with IL-1beta up-regulated the secretion of TNF-alpha, IL-6, IL-8, and MCP-1. CONCLUSION: IL-20 induces proinflammatory, chemotaxtic, and matrix degradative responses in IVD cells especially in combination with IL-1beta. Our study suggests that IL-20 plays an important role in the pathogenesis of disc herniation.
16: Biochemical and biophysical research communications, 2008 Sep 26, 374(3)
Interleukin-20 targets renal cells and is associated with chronic kidney disease.
[Abstract]Interleukin (IL)-10 is an anti-inflammatory factor that suppresses renal fibrosis and improves renal function in CKD rats. IL-20 belongs to the IL-10 family; therefore, we sought to determine whether IL-20 is involved in CKD. CKD patients at stage five expressed significantly higher IL-20 in serum than controls. Immunohistochemical staining demonstrated that more IL-20 protein was expressed in the kidney tubular-epithelial cells, mesangial cells, and immune cells of CKD rats with a 5/6 nephrectomy. The lung, liver, and heart tissue of CKD rats also overexpressed IL-20. Thus, we treated two tubular epithelial cells, TKPTS and M-1 cells, with IL-20 to study its effects on CKD. IL-20 treatment induced apoptosis in these cells via caspase-3 activation. Incubating IL-20 with rat interstitial fibroblasts, NRK-49F cells, upregulated TGF-beta1 production, one key inducer for renal fibrogenesis. Therefore, IL-20 injured renal epithelial cells and induced fibroblasts to produce TGF-beta1 that hastened the progression of CKD.
17: Genes and immunity, 2008 Jul, 9(5)
Interleukin-20 induced cell death in renal epithelial cells and was associated with acute renal failure.
[Abstract]Acute renal failure is an abrupt decrease in renal function. Interleukin (IL)-10 inhibits ischemic and cisplatin-induced acute renal failure. We aimed to determine whether IL-20 affects renal tubular epithelial cells and is associated with acute renal failure. We analyzed the expression of IL-20 and its receptor (R) in the kidneys of rats with HgCl(2)-induced acute renal failure. Reverse transcription-PCR showed upregulated IL-20, and its receptors and immunohistochemical staining showed strongly expressed IL-20 protein in proximal tubular epithelial cells. We analyzed human proximal tubular epithelial (HK-2) cells, which expressed both IL-20 and its receptors. IL-20 specifically induced mitochondria-dependent apoptosis by activating caspase 9 in HK-2 cells. IL-20 also activated c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2, the downstream signals implicated in the apoptosis of HK-2 cells. Furthermore, IL-20 upregulated the transcripts of transforming growth factor (TGF)-beta1, a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1 beta transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-beta1 and IL-1 beta and the number of damaged tubular cells in the kidneys of rats with acute renal failure. We concluded that IL-20 may be involved in the injury of renal epithelial cells in acute renal failure.
18: Cytokine, 2008 Jan, 41(1)
The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy.
[Abstract]The purpose of this study was to analyze the expression of the two proinflammatory cytokines IL-20 and IL-24 and their shared receptors in rheumatoid arthritis and spondyloarthropathy. IL-20 was increased in plasma of rheumatoid arthritis patients compared with osteoarthritis patients and IL-24 was increased in synovial fluid and plasma of rheumatoid arthritis and spondyloarthropathy patients compared with osteoarthritis patients. IL-20 and IL-24 mRNA was only present at low levels in the synovium. In the synovial membrane, IL-20 protein was present in mononuclear cells and neutrophil granulocytes whereas IL-24 protein was observed in endothelial cells and mononuclear cells. IL-20 receptor type 1 and IL-22 receptor were expressed by granulocytes in the synovial fluid. In synovial fluid mononuclear cell cultures, stimulation with recombinant human IL-20 or recombinant human IL-24 induced monocyte chemoattractant protein 1 (CCL2/MCP-1) secretion, but not tumour necrosis factor alpha mRNA synthesis or IL-6 secretion. Both IL-20 and IL-24 showed correlations to CCL2/MCP-1 in plasma from rheumatoid arthritis and spondyloarthropathy patients. This study associates IL-20 and IL-24 to the synovium of rheumatoid arthritis and spondyloarthropathy and results indicate that the two cytokines contribute to disease pathogenesis through recruitment of neutrophil granulocytes and induction of CCL2/MCP-1.