Renal expression of IL-6 and TNFα genes in lupus nephritis

Herrera‐Esparza, Rafael; Barbosa-Cisneros, O; Villalobos-Hurtado, R; Avalos‐Díaz, Esperanza

doi:10.1191/096120398678919949

Cited by 147 publications

(101 citation statements)

References 21 publications

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“…time course of renal MIF expression parallels the reported up-regulation of other key inflammatory cytokines and chemokines (21)(22)(23)(24)(25)(26). For example, TNF mRNA expression was markedly up-regulated in 24-wk-old MRL/lpr mice compared with 8-wk-old mice, and not detectable in similarly aged MRL ϩ/ϩ mice (22).…”

Section: Mif Expression In Mrl/lpr Micementioning

confidence: 49%

“…In addition, MIF released by macrophages can act in an autocrine and paracrine fashion to amplify the inflammatory response, by inducing the expression of a variety of proinflammatory cytokines such as TNF and IL-6 (46,52). Infiltrating mononuclear cells are the major source of TNF and IL-6 in diseased kidneys affected by lupus nephritis (22,24). The current data, indicating a trend toward reductions in renal TNF and IL-6 in MIF Ϫ/Ϫ MRL/lpr mice, suggest that in addition to a role for MIF in promoting renal macrophage accumulation, MIF may also act to regulate cytokine expression in infiltrating macrophages.…”

Section: Discussionmentioning

confidence: 60%

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Macrophage Migration Inhibitory Factor Deficiency Attenuates Macrophage Recruitment, Glomerulonephritis, and Lethality in MRL/lpr Mice

Hoi

Hickey

Hall

et al. 2006

The Journal of Immunology

125

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Systemic lupus erythematosus (SLE) is a serious systemic autoimmune disease of unknown etiology. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is operative in innate and adaptive immunity and important in immune-mediated diseases such as rheumatoid arthritis and atherosclerosis. The functional relevance of MIF in systemic autoimmune diseases such as SLE is unknown. Using the lupus-prone MRL/lpr mice, we aim to examine the expression and function of MIF in this murine model of systemic autoimmune disease. These experiments revealed that renal MIF expression was significantly higher in MRL/lpr mice compared with nondiseased control mice (MRL/MpJ), and MIF was also markedly up-regulated in skin lesions of MRL/lpr mice. To examine the effect of MIF on development of systemic autoimmune disease, we generated MRL/lpr mice with a targeted disruption of the MIF gene (MIF−/−MRL/lpr), and compared their disease manifestations to MIF+/+MRL/lpr littermates. MIF−/−MRL/lpr mice exhibited significantly prolonged survival, and reduced renal and skin manifestations of SLE. These effects occurred in the absence of major changes in T and B cell markers or alterations in autoantibody production. In contrast, renal macrophage recruitment and glomerular injury were significantly reduced in MIF−/−MRL/lpr mice, and this was associated with reduction in the monocyte chemokine MCP-1. Taken together, these data suggest MIF as a critical effector of organ injury in SLE.

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Section: Mif Expression In Mrl/lpr Micementioning

confidence: 49%

Section: Discussionmentioning

confidence: 60%

Macrophage Migration Inhibitory Factor Deficiency Attenuates Macrophage Recruitment, Glomerulonephritis, and Lethality in MRL/lpr Mice

Hoi

Hickey

Hall

et al. 2006

The Journal of Immunology

125

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“…We have reported previously that urinary levels of IL-6 correlated with lupus activity, and that these elevated levels decreased after treatment [29]. Herrera-Esparza et al demonstrated IL-6 mRNA in infiltrating mononuclear cells of glomeruli and renal interstitium by in situ hybridization [12]. Furthermore, studies have also shown that cultured mesangial cells produce IL-6, and that IL-6 induced mesangial cell proliferation [11].…”

Section: Discussionmentioning

confidence: 97%

“…Interleukin-6 (IL-6) is normally produced by monocytes, and mediates the late phase of B cell maturation [3,4,10]. In lupus nephritis (LN), the presence of interluekin-1 (IL-1), IL-6 and tumour necrosis factor-alpha (TNF-a ) in diseased kidneys also appears to mediate local pathogenic effects such as mesangial proliferation [11,12]. Furthermore, the clinical course and renal involvement in SLE can be significantly altered by the addition of cytokines or cytokine inhibitors [2,5,6].…”

Section: Introductionmentioning

confidence: 99%

Imbalance between interleukin-6 and adrenomedullin mRNA levels in peripheral blood mononuclear cells of patients with lupus nephritis

Nishitani

Kubo

Iwano

et al. 2001

Clinical and Experimental Immunology

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SUMMARYIn this study, we measured the mRNA levels of adrenomedullin (AM), C-type natriuretic peptide, vascular endothelial growth factor, interleukin-1b (IL-1b ) and interleukin-6 (IL-6) in peripheral blood mononuclear cells (PBMC) of 34 patients with lupus nephritis (LN) (15 active and 19 inactive) and 30 healthy volunteers. mRNA levels were measured using a real-time quantitative PCR method. Compared with healthy volunteers, IL-6 mRNA levels were elevated in LN patients (P , 0´005), while AM mRNA levels were decreased (P , 0´05). Also, IL-6 mRNA levels were higher and AM mRNA levels lower in active LN patients compared with inactive LN patients. In addition, IL-6 mRNA levels positively correlated and AM mRNA levels negatively correlated with SLE disease activity index and laboratory findings, such as blood urea nitrogen, serum creatinine, 50% haemolytic unit of complement and urinary excretion of protein over 24 h. Furthermore, IL-6 mRNA levels were negatively correlated with AM mRNA levels within the same LN patients. With regard to pathological findings, our results showed that IL-6 mRNA levels were higher, and AM mRNA levels significantly lower in patients with a high activity index compared to those with a low activity index. Following treatment with prednisolone, IL-6 mRNA levels in active LN patients decreased and AM mRNA levels increased to levels comparable to those in inactive LN and healthy volunteers. In vitro studies further demonstrated that elevated IL-6 mRNA levels in active LN patient PBMC were suppressed by the addition of adrenomedullin. Our results suggest that an imbalance between IL-6 and AM levels may play an important role in the progression of SLE, and that the mRNA levels of these genes in PBMC may be used as a disease activity index for SLE.

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“…33,34 IL-6 is expressed by tubuloepithelial cells in human acute and chronic renal disease. 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.…”

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

114

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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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Renal expression of IL-6 and TNFα genes in lupus nephritis

Cited by 147 publications

References 21 publications

Macrophage Migration Inhibitory Factor Deficiency Attenuates Macrophage Recruitment, Glomerulonephritis, and Lethality in MRL/lpr Mice

Macrophage Migration Inhibitory Factor Deficiency Attenuates Macrophage Recruitment, Glomerulonephritis, and Lethality in MRL/lpr Mice

Imbalance between interleukin-6 and adrenomedullin mRNA levels in peripheral blood mononuclear cells of patients with lupus nephritis

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

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