Complement gene expression is regulated by pro-inflammatory cytokines and the anaphylatoxin C3a in human tenocytes

Busch, Catharina; Girke, Georg; Kohl, Benjamin; Stoll, Christiane; Lemke, Marion; Krasnici, Senat; Ertel, Wolfgang; Silawal, Sandeep; John, Thilo; Schulze‐Tanzil, Gundula

doi:10.1016/j.molimm.2012.09.001

Cited by 15 publications

(17 citation statements)

References 31 publications

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“…However, DF3016A treatment restores the control situation, with the expression of C5a maintaining the unchanged levels of the protein in OGD/R-treated neurons. As shown by different authors (Sayah et al 1999 ; Song et al 2018 ), C5a protein binding to its receptor can lead to the production of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 which in turn affect complement expression (Busch et al 2013 ). In keeping with these pieces of evidence, in our experimental model, we observed overexpression of the major pro-inflammatory cytokines in OGD/R-exposed cultures.…”

Section: Discussionmentioning

confidence: 99%

The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury

et al. 2019

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The central nervous system (CNS) constitutively expresses complement (C) membrane receptors and complement proteins, including the component C5a. This is a crucial terminal effector of the C cascade, mostly involved in pain and neuroinflammatory conditions. Aberrant activation of C5a protein and its receptor C5aR has been reported to play a critical role in neurodegenerative diseases, with important clinical consequences. Here we have investigated the effects of DF3016A, a novel selective C5aR antagonist, able to penetrate the blood-brain barrier (BBB), on cortical neurons exposed to oxygen-glucose deprivation-reoxygenation (OGD/R), a neuroinflammation-related process. We demonstrated that a mild ischemic insult induces an early upregulation of C5aR associated with the over-production of pro-inflammatory cytokines and the over-expression of the transcriptional regulatory factor miR-181. Furthermore, we report the first experimental evidence of the effect of DF3016A, modulating complement component C5a, on neurons in a model of injury. Interestingly, DF3016A protects neuronal viability by restoring intracellular calcium levels, thus opposing the increase in pro-inflammatory cytokine levels and miR-181 expression. Based on our results, we suggest that DF3016A is a novel C5aR antagonist promoting protective effects against OGD/R-induced damage that could be a new therapeutic approach to controlling CNS neuroinflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury

et al. 2019

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“…We speculate that the joint C3–C3aR down-regulation might be a protective mechanism set into motion with the development of excess adiposity, and an attempt at protection against obesity-related complications. Acutely, C3a increases both C3aR and C3 [50], [51], however chronic stimulation with high circulating levels, as in obesity, may lead to negative feedback down-regulation, although the precise mechanism by which this is achieved is unknown.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Complement C3 and C3aR Expression in Subcutaneous Adipose Tissue in Obese Women

et al. 2014

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BackgroundThe central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease however the underlying reasons are unknown. In the present study we evaluated gene expression of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in subcutaneous and omental adipose tissue in women.MethodsWomen (n = 140, 21–69 years, BMI 19.5–79 kg/m2) were evaluated for anthropometric and blood parameters, and adipose tissue gene expression.ResultsSubjects were separated into groups (n = 34–36) according to obesity: normal/overweight (≤30 kg/m2), obese I (≤45 kg/m2), obese II (≤51 kg/m2), and obese III (≤80 kg/m2). Overall, while omental expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased with increasing adiposity (2-way ANOVA, p<0.01), with a concomitant decrease in SC/OM ratio (p<0.001). In subcutaneous adipose, both C3 and C3aR expression correlated with apoB, and apoA1 and inversely with waist circumference and blood pressure, while C3aR also correlated with glucose (p<0.05–0.0001). While omental C3aR expression did not correlate with any factor, omental C3 correlated with waist circumference, glucose and apoB (all p<0.05). Further, while plasma C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both correlated (C3a negatively and adiponectin positively) with subcutaneous C3 and C3aR expression (p<0.05–0.001) or less).ConclusionsThe obesity-induced down-regulation of complement C3 and C3aR which is specific to subcutaneous adipose tissue, coupled to the strong correlations with multiple anthropometric, plasma and adipokine variables support a potential role for complement in immunometabolism.

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“…Values are expressed as means ± SD (n = 3), and values with different lower case in superscript are significantly different at p < .05; 0, 0.1%, 0.2% and 0.4% yam extract group were denoted as Con, O1, O2 and O3 respectively [Colour figure can be viewed at wileyonlinelibrary.com] the intestinal flora, and some of them promote the secretion of lysozyme to modulate complement components activation (Meng et al, 2019;Ogundele, 1998). The production of complement components is regulated by proinflammatory cytokines (Busch et al, 2013). Therefore, TNF-α, IL-6 and IL-2 levels in serum and TNF-α mRNA expression in intestine of yam extract groups were significantly increased.…”

Section: F I G U R Ementioning

confidence: 99%

Effects of Chinese yam ( Dioscorea oppositifolia L .) dietary supplementation on intestinal microflora, digestive enzyme activity and immunity in rainbow trout ( Oncorhynchus mykiss )

Wang

Liu

et al. 2020

Aquac Res

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The intensive and semi-intensive cultivation is widely used in aquaculture and easily causes disease outbreaks bringing about the loss of aquatic products. Furthermore, factors including overcrowding, sudden changes of temperature, the deterioration of water quality, and inadequate feeding and management could result in immunosuppression in aquatic animals and thus increasing the susceptibility to certain infectious diseases (Awad & Awaad, 2017). In order to prevent and cure the infectious diseases, some antimicrobials have been extensively used in aquaculture industries. However, antibiotics and some chemotherapy treating diseases inevitably lead to

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Complement gene expression is regulated by pro-inflammatory cytokines and the anaphylatoxin C3a in human tenocytes

Cited by 15 publications

References 31 publications

The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury

The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury

Downregulation of Complement C3 and C3aR Expression in Subcutaneous Adipose Tissue in Obese Women

Effects of Chinese yam ( Dioscorea oppositifolia L .) dietary supplementation on intestinal microflora, digestive enzyme activity and immunity in rainbow trout ( Oncorhynchus mykiss )

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