Elevated levels of soluble CD 14 in serum of patients with systemic lupus erythematosus

Nockher, Wolfgang Andreas; Wigand, R.; Schoeppe, W.; Scherberich, Jürgen E.

doi:10.1111/j.1365-2249.1994.tb06222.x

Cited by 105 publications

(55 citation statements)

References 31 publications

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“…It has been reported that various plasma components may interfere with detection of LPS by the LAL test (31,32). Finally, CD14 is a multifunctional receptor molecule that responds to endotoxin from gram-negative bacteria and multiple other ligands (19,33), possibly confounding the relationship between plasma endotoxin and sCD14, in which sCD14 may be better considered a general marker of monocyte activation (34).…”

Section: Discussionmentioning

confidence: 99%

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD

Poesen

Ramezani

Claes

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD.Design, setting, participants, & measurements We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR,60 ml/min per 1.73 m 2 for $3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006.Results Plasma sCD14 was negatively associated with eGFR (r=-0.34, P,0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P,0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (r=-0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up.Conclusions Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.

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Section: Discussionmentioning

confidence: 99%

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD

Poesen

Ramezani

Claes

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…19 Serum levels of sCD14 are increased in some systemic autoimmune diseases, especially lupus, rheumatoid arthritis and Kawasaki syndrome. 15,[20][21][22][23] Correlations between increased sCD14 levels, lupus disease activity and lupus nephritis have been described in adult patients. 20,21 Therefore, in order to add information about monocyte role in JSLE development, we evaluated the expressions of Fas and Bcl-2 proteins in CD14þ monocytes, measured sCD14 serum levels and analyzed the relationships with lupus nephritis and lupus disease activity.…”

Section: Introductionmentioning

confidence: 99%

Reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes and normal CD14 soluble levels in juvenile systemic lupus erythematosus

Liphaus

Kiss

Carrasco

et al. 2013

Lupus

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In order to evaluate Fas and Bcl-2 expressions in CD14+ monocytes, to measure soluble CD14 serum levels and to analyze the relationships with lupus nephritis and disease activity, we enrolled 41 patients with juvenile systemic lupus erythematosus (JSLE) and 27 healthy volunteers. Disease activity was determined by SLEDAI score. Peripheral monocytes were stained for CD14, Fas and Bcl-2 molecules, and cellular expressions were determined by flow cytometry. Soluble CD14 levels were measured by a quantitative ELISA kit. JSLE patients, those with active disease and those with nephritis, presented significantly reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes compared with healthy controls. Significant inverse correlations between percentages of CD14+Fas+ cells, SLEDAI score and anti-dsDNA antibodies were observed. JSLE patients had soluble CD14 levels similar to controls, although sCD14 levels positively correlated with ESR, but not with SLEDAI score. JSLE patients with nephritis also presented sCD14 levels similar to controls. In conclusion, the reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes from JSLE patients depict that monocyte apoptotic mechanisms may be important in lupus pathogenesis.

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“…It has been shown that sCD14 is an acute phase protein (Bas et al 2004). Clinical studies have shown that plasma level of sCD14 is elevated in a number of inflammatory diseases such as rheumatoid arthritis (Yu et al 1998), systemic lupus erythematosus (Nockher et al 1994), atopic dermatitis (Wuthrich et al 1992), liver disease (Oesterreicher et al 1995), Kawasaki disease (Takeshita et al 2000), and atherosclerosis (Amar et al 2003). Membrane-bound CD14 expression by mononuclear cells as determined by flow cytometry was found to be higher in diabetic patients than that in non-diabetic patients (Patino et al 2000, Fogelstrand et al 2004.…”

Section: Introductionmentioning

confidence: 99%

High glucose enhances lipopolysaccharide-stimulated CD14 expression in U937 mononuclear cells by increasing nuclear factor κB and AP-1 activities

Nareika

Im²,

Game³

et al. 2007

Journal of Endocrinology

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We have demonstrated recently that high glucose augments lipopolysaccharide (LPS)-stimulated matrix metalloproteinase (MMP) and cytokine expression by U937 mononuclear cells and human monocyte-derived macrophages. Since CD14 is a receptor for LPS, one potential underlying mechanism is that high glucose enhances CD14 expression. In the present study, we determined the effect of high glucose on CD14 expression by U937 mononuclear cells. After being chronically exposed to normal or high glucose for 2 weeks or longer, cells were treated with LPS for 24 h. Real-time PCR showed that although high glucose by itself did not increase CD14 expression significantly, it augmented LPS-stimulated CD14 expression by 15-fold. Immunoassay showed a marked enhancement of both membrane-associated and soluble CD14 protein levels by high glucose. Further investigations using transcription factor activity assays and gel shift assays revealed that high glucose augmented LPS-stimulated CD14 expression by enhancing transcription factor nuclear factor kB (NFkB) and activator protein-1 (AP-1) activities. Finally, studies using anti-CD14 neutralizing antibody showed that CD14 expression is essential for the enhancement of LPS-stimulated MMP-1 expression by high glucose. Taken together, this study has demonstrated a robust augmentation by high glucose of LPS-stimulated CD14 expression through AP-1 and NFkB transcriptional activity enhancement, elucidating a new mechanism by which hyperglycemia boosts LPS-elicited gene expression involved in inflammation and tissue destruction.

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Elevated levels of soluble CD 14 in serum of patients with systemic lupus erythematosus

Cited by 105 publications

References 31 publications

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD

Reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes and normal CD14 soluble levels in juvenile systemic lupus erythematosus

High glucose enhances lipopolysaccharide-stimulated CD14 expression in U937 mononuclear cells by increasing nuclear factor κB and AP-1 activities

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