Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells.

Brooimans, Ricardo A.; Stegmann, Alexander P.A.; Dorp, W.T. van; Ark, Arno A. J. van der; Woude, Fokko J. van der; Es, Leendert A. van; Daha, Mohamed R.

doi:10.1172/jci115314

Cited by 179 publications

(108 citation statements)

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“…All in all, the balance between the degree of production of IL-1 , TNF-and IFN-at the local site may determine the final outcome of the inflammation by fine regulation of the production of IL-8 or other chemotactic cytokines or complement components at the local site [16][17][18][19]35]. In case of upregulation of IL-8, the influx of neutrophils may lead to an increase of the local inflammation.…”

Section: Discussionmentioning

confidence: 99%

Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro

Gerritsma¹,

Hiemstra

Gerritsen³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYA number of inflammatory kidney diseases are associated with interstitial nephritis and influx of leucocytes in the renal interstitium. Potentially the influx of neutrophils in the interstitium may be induced by the chemotactic cytokine IL-8. In the present study we have analysed the production of IL-8 by cultured human proximal tubular epithelial cells (PTEC) in response to a number of proinflammatory cytokines. Primary cell lines of proximal tubular epithelium obtained from ten different kidneys, and cultured under serum-free conditions, were found to produce IL-8 to different degrees from not detectable levels up to 10

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Section: Discussionmentioning

confidence: 99%

Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro

Gerritsma¹,

Hiemstra

Gerritsen³

et al. 1996

Clinical and Experimental Immunology

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“…4), it is most likely that C3 is activated and coupled to viral Ags within the local lymph node that drains the site of infection. Although the regulation of C3 synthesis by macrophages in vivo is not known, studies with human and murine cell lines indicate that C3 secretion can be induced by multiple cytokines such as IFN-␥ (46, 47), IL-6 (48), TNF (38), IL-1 (49), and IL-2 (40). Macrophages secrete other components of complement in addition to C3 and in particular C4, C2, C1r, C1s, and C1q (36,50,51).…”

Section: Figure 2 Infectious Hsv-1 Induces Significantly Greater Ab mentioning

confidence: 99%

“…However, a number of extrahepatic sources of C3 synthesis have been described. These include myeloid lineage cells such as monocytic cells (36) and polymorphonuclear leukocytes (37) as well as non-bone marrow (non-BM)-derived sources such as epidermal keratinocytes (38), kidney tubular epithelial cells (39,40), and umbilical vein endothelial cells (41). The potential of macrophage-derived C3 in the humoral response to protein Ag was determined using C3 Ϫ/Ϫ BM chimeras that received wild-type (WT) BM (WT BM3 C3 Ϫ/Ϫ ).…”

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confidence: 99%

Cutting Edge: Myeloid Complement C3 Enhances the Humoral Response To Peripheral Viral Infection

Verschoor

Brockman

Knipe

et al. 2001

The Journal of Immunology

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HSV-1 is the causative agent of cutaneous lesions, commonly referred to as cold sores. Primary exposure to the virus ordinarily occurs through the periphery, in particular through abraded skin or mucosal membranes. Under certain circumstances (e.g., in neonatals or AIDS patients), the infection becomes disseminated, often with severe consequences. Spread of HSV-1 is limited by virus-specific Ab. The development of an efficient humoral response to the virus is dependent on innate immunity component complement C3. The liver is the major source of C3, but there are also extrahepatic origins of C3 such as lymphoid macrophages. In the present study, the significance of C3 synthesis by bone marrow-derived cells was assessed by the transfer of wild-type bone marrow into irradiated C3-deficient mice. Using these chimeric mice, extrahepatic C3 was determined sufficient to initiate specific Ab and memory responses to a peripheral HSV-1 infection.

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“…The alternative sites for complement production include epithelial cells, fibroblasts, lymphocytes and macrophages derived from different organs, including the kidney [14] . In the kidney, local complement production has been shown to occur at different sites along the nephron and may be further enhanced by the presence of cytokines and infiltrating immune cells during acute inflammation [15][16][17] . …”

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confidence: 99%

Complement activation in progressive renal disease

Fearn

Sheerin

2015

WJN

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ritis, thrombotic microangiopathies and transplant reje ction. In this review we discuss current evidence that complement activation contributes to progression of CKD, how complement could cause renal inflammation and whether complement inhibition would slow progression of renal disease. Core tip: Complement activation occurs in progressive chronic kidney disease and may contribute to the chronic inflammation that is characteristically found in the kidney. It is therefore possible that inhibiting complement activation would reduce inflammation, lead to reduced fibrosis and preservation of renal function. INTRODUCTIONChronic kidney disease (CKD) is recognised worldwide as a major public health problem [1] . In 2007 the United Kingdom age-standardised prevalence of CKD stages 3-5 was 8.5% (10.6% in females and 5.8% in males) [2] and similar prevalences have been described in other countries. In 2012 in the United Kingdom, the number of new patients requiring renal replacement therapy was 6891, equating to 108 patients per million population, with diabetes and glomerulonephritis being the two most common diagnoses in incident dialysis patients. Although not all patients with CKD will progress to renal failure, all stages of CKD are associated with increased AbstractChronic kidney disease (CKD) is common and the cause of significant morbidity and mortality. The replacement of functioning nephrons by fibrosis is characteristic of progressive disease. The pathways that lead to fibrosis are not fully understood, although chronic nonresolving inflammation in the kidney is likely to drive the fibrotic response that occurs. In patients with progressive CKD there is histological evidence of inflammation in the interstitium and strategies that reduce inflammation reduce renal injury in preclinical models of CKD. The complement system is an integral part of the innate immune system but also augments adaptive immune responses. Complement activation is known to occur in many diverse renal diseases, including glomeruloneph morbidity and mortality [1] . Tubulointerstitial inflammation and fibrosis is a major factor in the progressive loss of renal function in most kidney diseases [3] . The process is complex due to the number of interacting pathways which ultimately result in the replacement of functioning nephrons with scar tissue. Cellular stress and injury induces an inflammatory and pro-fibrogenic response involving growth factors [4][5][6] and pro-inflammatory cytokines as well as activation of the renin-angiotensin system. This leads to a chronic inflammatory cell infiltrate, increasing numbers of activated fibroblasts (myofibroblasts) and excessive matrix deposition. There is evidence from preclinical models that the immune system is important in the development of renal fibrosis [7,8] . A component of the innate immune system that may be important in driving renal inflammation is the complement system, which can directly affect cell function and also influence the adaptive immune response. REVIEW COMPLEMENT SYSTEMTh...

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Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells.

Cited by 179 publications

References 32 publications

Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro

Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro

Cutting Edge: Myeloid Complement C3 Enhances the Humoral Response To Peripheral Viral Infection

Complement activation in progressive renal disease

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