Elevated serum complement factors 3 and 4 are strong inflammatory markers of the metabolic syndrome development: a longitudinal cohort study

Liu, Zhenfang; Tang, Qin; Wen, Jing; Tang, Yan; Huang, Damin; Huang, Yuzhen; Xie, Jinling; Luo, Yue; Liang, Min; Wu, Chunlei; Lu, Zheng; Tan, Aihua; Gao, Yong; Wang, Qiuyan; Jiang, Yonghua; Yao, Ziting; Lin, Xinggu; Zhang, Haiying; Mo, Zengnan; Yang, Xiaobo

doi:10.1038/srep18713

Cited by 45 publications

(44 citation statements)

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“…Activation of the complement system is an important part of an inflammatory process, as elevated serum C3 and C4 are strong inflammatory markers (Liu et al, ). The present data suggest that sperm can activate the local complement system in BUECs, as demonstrated by increased C3 mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

A proinflammatory response of bovine endometrial epithelial cells to active sperm in vitro

Elweza

Ezz

Acosta

et al. 2018

Molecular Reproduction Devel

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In the cow, cryopreserved semen is inseminated into the uterus, and most of sperm are removed by backflow and phagocytes. Nevertheless, the mechanism responsible for sperm phagocytosis is unclear. Here, we used cultured bovine uterine epithelial cells (BUECs) to investigate the uterine response to sperm and the mechanism that activates polymorphonuclear neutrophils (PMNs). BUEC monolayers were co-cultured with different numbers of washed sperm obtained from cryopreserved semen (10 , 10 , and 10 sperm/ml) for 3 hr. Sperm dose-dependently up-regulated IL8 (Interleukin 8). Sperm at 10 /ml increased mRNA expression of TNFA (Tumor necrosis factor alpha), IL1B (Interleukin 1B), NFKB2 (Nuclear factor kappa B2), and C3 (Complement factor 3), as well as PGES (Prostaglandin E synthase) expression and PGE release. Live sperm, but not dead sperm, attached to BUECs, and dead sperm did not induce an acute inflammatory response. Time-dependent effects were evaluated by co-culture of 10 /ml washed sperm with BUECs for 0, 1, 3, and 6 hr. The number of detached sperm increased gradually toward 6 hr. Maximum mRNA expression of IL8, TNFA, IL1B, and NFKB2 was induced at 3 hr, while C3 continued to increase toward 6 hr. Sperm did not stimulate mRNA expression of anti-inflammatory cytokines TGFB1 (Transforming growth factor beta 1) or IL10 (Interleukin 10). Medium conditioned by sperm co-incubated with BUECs stimulated PMNs phagocytosis of sperm in vitro. Fresh media supplemented with low levels of IL1B, TNFA, and PGE up-regulated sperm phagocytosis by PMNs as well. In conclusion, our findings strongly suggest that the active sperm attach to BUECs and trigger uterine local innate immunity with induction of a pro-inflammatory response that enhances sperm phagocytosis by PMNs.

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Section: Discussionmentioning

confidence: 99%

A proinflammatory response of bovine endometrial epithelial cells to active sperm in vitro

Elweza

Ezz

Acosta

et al. 2018

Molecular Reproduction Devel

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“…Complement underlies not only one of the effector mechanisms of antibody‐mediated immunity but also constitutes one of the host's acute‐phase reactions . Recently, an increasing number of studies have shown that elevated serum C3 and C4 levels are useful markers of inflammation . Doi et al .…”

Section: Discussionmentioning

confidence: 99%

“…Elevated serum C3 and C4 levels are found in patients with Crohn's disease and ulcerative colitis . Furthermore, elevated C3 and C4 levels are not only strong inflammatory markers of metabolic syndrome development, but are also independent risk factors for metabolic syndrome development . Although Martinez‐Hernandez et al .…”

Section: Discussionmentioning

confidence: 99%

“…Complement underlies not only one of the effector mechanisms of antibody-mediated immunity but also constitutes one of the host's acute-phase reactions [19]. Recently, an increasing number of studies have shown that elevated serum C3 and C4 levels are useful markers of inflammation [9,11,12,[20][21][22][23][24]. Doi et al [9] considered that hypercomplementemia in anti-aquaporin 4 antibody-positive patients may reflect a systemic inflammatory reaction at relapse.…”

Section: Discussionmentioning

confidence: 99%

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Serum complement levels in anti‐N‐methyl‐d‐aspartate receptor encephalitis

Shu

Chen

et al. 2017

Euro J of Neurology

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“…They have been shown to increase the levels of CRP, TG and fibrinogen. Increased plasma levels of circulating sC5b-9 complex have been shown to be inversely correlated with the concentration of HDL-C (Pasqui et al, 2000;Onat et al, 2005;Liu et al, 2016); Figure 1A). Inflammation also results in increased secretion of secretory PLA 2 (sPLA2) from various tissues.…”

Section: Figurementioning

confidence: 99%

Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

Iqbal

Baker

Khan

et al. 2017

British J Pharmacology

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Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Inflammatory processes arising from metabolic abnormalities are known to precipitate the development of CVD. Several metabolic and inflammatory markers have been proposed for predicting the progression of CVD, including high density lipoprotein cholesterol (HDL-C). For~50 years, HDL-C has been considered as the atheroprotective 'good' cholesterol because of its strong inverse association with the progression of CVD. Thus, interventions to increase the concentration of HDL-C have been successfully tested in animals; however, clinical trials were unable to confirm the cardiovascular benefits of pharmaceutical interventions aimed at increasing HDL-C levels. Based on these data, the significance of HDL-C in the prevention of CVD has been called into question. Fundamental in vitro and animal studies suggest that HDL-C functionality, rather than HDL-C concentration, is important for the CVD-preventive qualities of HDL-C. Our current review of the literature positively demonstrates the negative impact of systemic and tissue (i.e. adipose tissue) inflammation in the healthy metabolism and function of HDL-C. Our survey indicates that HDL-C may be a good marker of adipose tissue health, independently of its atheroprotective associations. We summarize the current findings on the use of antiinflammatory drugs to either prevent HDL-C clearance or improve the function and production of HDL-C particles. It is evident that the therapeutic agents currently available may not provide the optimal strategy for altering HDL-C metabolism and function, and thus, further research is required to supplement this mechanistic approach for preventing the progression of CVD. LINKED ARTICLES IntroductionThere have been several sharp turns in the evidence trail marking the atheroprotective role of high density lipoproteins (HDLs). Very early studies on dyslipidaemia highlighted the positive correlation between total triglycerides (TGs) with the risk of developing cardiovascular disease (CVD). Since the mid-1970s, numerous epidemiological and animal studies, including the Framingham Study (Gordon et al., 1977), reported that HDL cholesterol (HDL-C) has the strongest inverse relationship with the development of CVD of the known serum lipid factors (Badimon et al., 1990;Rubin et al., 1991;Liu et al., 1994;Plump et al., 1994). This association is underpinned by reverse cholesterol transport (RCT) -a process by which HDL-C transfers the cholesterol from peripheral cells, for example, lipid-laden foam cells, to the liver for secretion into bile and faeces. The promotion of RCT is considered a major anti-atherogenic function of HDL-C (Gofman et al., 1966;Miller and Miller, 1975;Rhoads et al., 1976). Based on these findings, interventions to increase the levels of HDL-C were developed but found to be ineffective for preventing cardiovascular outcomes in several large clinical trials (Brousseau et al., 2004;McKenney et al., 2006;Barter et al., 2007;Boden et al., 2011;Lü...

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Elevated serum complement factors 3 and 4 are strong inflammatory markers of the metabolic syndrome development: a longitudinal cohort study

Cited by 45 publications

References 46 publications

A proinflammatory response of bovine endometrial epithelial cells to active sperm in vitro

A proinflammatory response of bovine endometrial epithelial cells to active sperm in vitro

Serum complement levels in anti‐N‐methyl‐d‐aspartate receptor encephalitis

Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

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