Caspase-1 Concentrations Research Articles

Increased serum caspase-1 in adult-onset Still's disease.

Caspase-1 is a crucial component in the inflammasome activation cascade. This study evaluated the potential of serum caspase-1 level as an inflammatory biomarker in patients with adult-onset Still's disease (AOSD). The study included 51 consecutive patients diagnosed with AOSD based on the Yamaguchi criteria, 66 patients with rheumatoid arthritis (RA) as disease control, and 36 healthy controls (HCs). Serum caspase-1 concentrations were measured using enzyme-linked immunosorbent assay. The serum 69 cytokine levels were analyzed using a multisuspension cytokine array in patients with AOSD, and a cluster analysis of each cytokine was performed to determine specific molecular networks. Patients with AOSD had significantly increased serum caspase-1 levels versus patients with RA (p < 0.001) and HCs (p < 0.001). Additionally, serum caspase-1 demonstrated significant positive correlations with AOSD disease activity score (Pouchot score, r = 0.59, p < 0.001) and serum ferritin (r = 0.54, p < 0.001). Furthermore, among patients with AOSD, significant correlations existed between serum caspase-1 and inflammatory cytokines, including interleukin-18. Immunoblot analysis detected the cleaved form of caspase-1 (p20) in the serum of untreated patients with AOSD, not in those from patients with inactive AOSD receiving immunosuppressive treatments. Caspase-1 is a useful biomarker for AOSD diagnosis and monitoring. Caspase-1 activation could be correlated with the inflammatory component of AOSD, specifically through proinflammatory cytokine induction via inflammasome activation cascades.

Electroacupuncture alleviates cognitive dysfunction and neuronal pyroptosis in septic mice.

Sepsis is defined as organ dysfunction caused by an uncontrolled response to infection and is followed by a high incidence of cognitive dysfunction, which can severely affect patients' quality of life. Previous studies have suggested that electroacupuncture (EA) is protective against sepsis-associated cognitive dysfunction and that pyroptosis plays a vital role in cognitive function. The aim of this study was to investigate the effect of EA on cognition and neuronal pyroptosis in a mouse model of sepsis. Sepsis was induced by cecal ligation and puncture (CLP) surgery. Mice were randomly divided into three groups (control, CLP and CLP + EA). EA was performed at bilateral ST36 for three consecutive days after the surgery. The 7-day survival rate of each group was observed on the seventh day after the surgery. The Morris water maze (MWM) was used to test cognitive function from the 8th to 12th day after the surgery. We used transmission electron microscopy (TEM) and transferase dUTP nick-end labeling (TUNEL) staining to determine the structural integrity of hippocampal neuronal membranes and the number of surviving neurons in the hippocampal tissues, respectively. Expression of nucleotide-binding domain-like receptor protein 1 (NLRP1), caspase-1 and gasdermin-D (GSDM D) in hippocampal CA1 neurons was detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and caspase-1 concentrations were measured by enzyme-linked immunosorbent assay. Compared with the CLP group, 7-day survival rates and cognitive function were significantly improved in the CLP + EA group. After EA treatment, the integrity of the hippocampal CA1 neuronal membrane and mortality of hippocampal neurons were significantly decreased, and expression of NLRP1, caspase-1 and GSDM D was downregulated. EA can alleviate cognitive dysfunction and neuronal pyroptosis in septic mice.

P-658 NLRP3 Inflammasome and polycystic ovarian syndrome – a possible novel association

Abstract Study question Is NLRP3 inflammasome expression in subcutaneous adipose tissue (SAT) and peripheral blood monocytes upregulated in women with polycystic ovarian syndrome (PCOS) compared to healthy controls? Summary answer NLRP3 expression was upregulated in subcutaneous adipose tissue but not in peripheral blood mononuclear cells (PBMCs) of women with PCOS compared to controls. What is known already Emerging evidence strongly suggests that PCOS is a chronic inflammatory condition. Inflammasomes are multiprotein complexes, which act as intracellular regulators of inflammation. It is now well established that NLRP3 inflammasome plays a central role in obesity-induced inflammation and insulin resistance. Given the close link between obesity and PCOS, it is plausible to hypothesize that the NLRP3 inflammasome may play a role in PCOS-related chronic inflammation and insulin resistance. This hypothesis has never been investigated before. Study design, size, duration This lab-based study involved reproductive age women (age 18–45years; BMI≤40kg/m2) who were diagnosed with PCOS (n = 24) according to the Rotterdam criteria. A healthy control group of non-PCOS women (n = 13) of similar age and BMI was included. Ethics approval was obtained, and all participants signed a written, informed consent. SAT biopsies were obtained during routine gynaecological surgery through the abdominal skin incision. Blood samples were obtained during surgery or during clinic visits. Participants/materials, setting, methods Blood samples were processed to separate plasma and to isolate peripheral blood mononuclear cells (PBMCs). SAT and PBMCs were analysed using qPCR and Western Blot (WB) to measure the relative gene and protein expression levels of NLRP3, CYP17, Caspase-1, IL-1β and IL-18 in both groups. ELISA was used to measure concentrations of Caspase-1, IL-1β and IL-18 in the plasma. Main results and the role of chance NLRP3 gene expression in SAT was significantly (p = 0.038) higher in PCOS women (2.08±3.5 (n = 12)) compared to controls (0.77±2.9 (n = 8)). Both groups were matched for age (PCOS, 29.4±3.7 vs controls, 30.3±4.0) and BMI (PCOS, 25.4±3.2 vs controls, 26.9±4.3). CYP17 expression was significantly (p = 0.001) higher in PCOS women (4.8±0.1) versus controls (1.5±1.6). There was a moderate positive correlation (r²=0.576, P &amp;lt; 0.05) between SAT NLRP3 and CYP17 expressions. NLRP3 gene expression in PBMCs were not significantly (p &amp;lt; 0.05) different between non-obese PCOS (-2.64±1.55 (n = 4)), obese PCOS (-2.847±1.85 (n = 8)) and non-PCOS women (0.000±2.67 (n = 5)). Using WB in PBMCs, NLRP3 band had a mean molecular weight of 72.59±5.43kDa with no significant difference between groups, with a trend towards higher levels in PCOS. Using ELISA in PBMCs, NLRP3 levels were not significantly (p = 0.3) different between PCOS (1.53±1.32pg/ml (n = 12)) vs controls (1.03±0.583 (n = 5)). Gene expression levels of Caspase-1, IL-1b and IL-18 in PBMCs were not significantly (P &amp;gt; 0.05) different between groups. Plasma IL-1β levels were significantly (p &amp;lt; 0.05) higher in PCOS (51.64±91.00ng/ml) vs. controls (0.47±0.93ng/ml). Plasma IL-18 concentrations were not significantly different between PCOS (3.79±0.53μg/ml) vs. controls (4.08±0.21μg/ml). Limitations, reasons for caution One limitation of this study is the lack of data on the protein expression of NLRP3 in the adipose tissue. There was also no data on other inflammasome components in the SAT analysis e.g. Caspase-1. However, all these data were available for the PBMCs. Wider implications of the findings The novel and interesting finding of an increase in NLRP3 in adipose tissue of PCOS women suggests that this inflammasome may play a central role in this common condition. Our study may therefore pave the way to further research to help understand the role of inflammation in PCOS Trial registration number N/A

Puerarin mitigates symptoms of depression in ovariectomized female rats by regulating hippocampal cAMP-CREB-BDNF signaling pathway

Purpose: To investigate the effect of puerarin on the symptoms of depression in ovariectomized female rat model, and the mechanism of action involved.&#x0D; Methods: Ninety healthy female Sprague Dawley (SD) rats were assigned to five groups: sham, model, low-dose puerarin, medium-dose puerarin, and high-dose puerarin groups, with 18 rats per group. Changes in the levels of dopamine (DA), norepinephrine (NA), 5-hydroxytryptamine (5-HT), and apoptosis-related proteins were determined and compared.&#x0D; Results: Compared with the sham group, vertical and horizontal scores, and levels of DA, NA, 5-HT, Bcl-2, p-CREB and BDNF in the model group were significantly decreased. On the other hand, duration of immobility in forced swimming was prolonged, while the concentrations of caspase-1 and ASC increased significantly (p &lt; 0.05). Compared with the model group, with increase in pueraria dose, vertical and horizontal scores, and expression levels of DA, NA, 5-HT, Bcl-2, p-CREB and BDNF of rats were gradually increased, duration of immobility in forced swimming was gradually shortened, and the expression levels of Caspase-1 and ASC w decreased gradually, relative to model group (p &lt; 0.05).&#x0D; Conclusion: Puerarin mitigates depression-like behavior of ovariectomized-depression rats by activating cAMP-CREB-BDNF signaling pathway. Thus, this compound is a potential new lead in the development of drugs for the treatment of depression in ovariectomized women.

Differential Impact of Weight Loss and Glycemic Control on Inflammasome Signaling.

Interleukin (IL)-1β is involved in obesity-associated inflammation and in the pathogenesis of type 2 diabetes (T2D) mellitus. Our aim was to correlate serum IL-1β and caspase-1 levels with weight loss, glucose metabolism, and insulin resistance (IR) after bariatric surgery. A total of 32 patients with morbid obesity and T2D (Ob-T2D) and 29 patients with morbid obesity and normal glucose tolerance (Ob-NGT), treated by Roux-en-Y gastric bypass, were studied before and 1 year after surgery. Sixteen healthy individuals served as a control (HC) group. IR was assessed by the oral glucose insulin sensitivity method. Plasma IL-1β levels and caspase-1 were measured. Presurgery BMI was similar in Ob-NGT and Ob-T2D. IR was progressively impaired in Ob-NGT and Ob-T2D (P < 0.0001). Fasting plasma IL-1β and caspase-1 levels were lower in HCs than in patients with Ob-NGT or Ob-T2D (P < 0.02; P = 0.05), and both were inversely correlated with IR (P = 0.01; P = 0.02). After surgery, BMI decreased and IR improved to a similar extent in Ob-NGT and Ob-T2D (P < 0.0001). Plasma caspase-1 concentrations normalized in both groups (P < 0.0001), whereas plasma IL-1β levels normalized only in Ob-NGT. Plasma IL-1β and caspase-1 levels were inversely correlated with IR. Caspase-1 levels normalized after weight loss, whereas IL-1β normalized only in people without T2D, suggesting the persistence of a systemic inflammatory condition in people with T2D.

P2X7R Blockade Prevents NLRP3 Inflammasome Activation and Pancreatic Fibrosis in a Mouse Model of Chronic Pancreatitis.

The aim of this study was to investigate the role of P2X7R (purinergic 2X7 receptor) and NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome activation in the process of pancreatic fibrosis in a mouse model of chronic pancreatitis (CP). Chronic pancreatitis was induced by repeated intraperitoneal injections of 50 μg/kg cerulein for 6 weeks in mice. P2X7R antagonist oxidized ATP (OxATP) or brilliant blue G (BBG) was administered after the last cerulein injection for 2 weeks. Pancreatic chronic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin immunohistochemical staining. We further determined pancreatic P2X7R, NLRP3, and caspase-1 expressions in gene and protein levels and the pancreatic concentrations of caspase-1, interleukin 1β (IL-1β), and IL-18. The pancreatic P2X7R, NLRP3, and caspase-1 expressions in gene and protein levels and the pancreatic concentrations of caspase-1, IL-1β, and IL-18 were all reduced significantly in both the OxATP and BBG groups (P < 0.05). The pancreatic chronic inflammation and the fibrosis indices were all remarkably attenuated (P < 0.05). P2X7R antagonist OxATP and BBG significantly decreased pancreatic chronic inflammation and fibrosis in a mouse CP model and suggested that blockade of P2X7R-NLRP3 inflammasome signaling pathway may represent a novel therapeutic strategy for CP and its fibrotic process.

MP70-09 INDICATORS OF INFLAMMASOME ACTIVATION IN MEN WITH ABNORMAL SEMEN PARAMETERS

You have accessJournal of UrologyInfertility: Basic Research & Pathophysiology1 Apr 2016MP70-09 INDICATORS OF INFLAMMASOME ACTIVATION IN MEN WITH ABNORMAL SEMEN PARAMETERS Emad Ibrahim, Karen Ibrahim, Michael Jurewicz, Teodoro Aballa, George Attia, Charles Lynne, and Nancy Brackett Emad IbrahimEmad Ibrahim More articles by this author , Karen IbrahimKaren Ibrahim More articles by this author , Michael JurewiczMichael Jurewicz More articles by this author , Teodoro AballaTeodoro Aballa More articles by this author , George AttiaGeorge Attia More articles by this author , Charles LynneCharles Lynne More articles by this author , and Nancy BrackettNancy Brackett More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1434AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Assembly of the inflammasome complex results in caspase-1 activation which promotes the maturation and secretion of the pro-inflammatory cytokines IL-1β and IL-18. Evidence of inflammasome activation and the consequent elevation of semen cytokines has been reported as a possible cause of abnormal semen quality in men with spinal cord injury (SCI) [Fertil Steril 2013;99:118-24, Hum Reprod 2014;29:2368-73]. This study sought to determine if indicators of inflammasome activation were evident in non-SCI men with abnormal semen parameters. METHODS Semen was obtained from men with abnormal semen parameters who were being evaluated in an infertility clinic (n=131). Each of these men was assigned to a group depending on his semen parameters. Oligo: men with low sperm concentration but normal sperm motility (n=29); Astheno: men with low sperm motility (<40%) but normal sperm concentration (≥20 million/cc) (n=14); Oligo+Astheno: men with combined low sperm concentration and low sperm motility (n=70); Terato: men with normal sperm count, normal sperm motility, but low sperm morphology (<4%) (n=8); Azo: men with no sperm in their ejaculate (n=10). Over 80% of the men in the Oligo, Astheno and Oligo+Astheno groups also had low sperm morphology. Semen from healthy normospermic men (n=10) served as control material. Seminal plasma was separated from semen by centrifugation and analyzed for caspase-1, IL-18, and IL-1β concentrations using ELISA (R&D Systems, Minneapolis, MN). Comparisons between controls and patient groups were made by student's t-test. Statistical significance was considered at p ≤ 0.05. RESULTS Caspase-1 concentrations were significantly elevated in all groups compared to controls. IL-1β concentrations were elevated in all groups compared to controls but reached statistical significance only in the Oligo+Astheno, and the Terato groups. IL-18 concentrations were also elevated in all groups compared to controls but reached statistical significance only in the Oligo+Astheno group. (Table 1). CONCLUSIONS This study shows elevation of inflammasome activation indicators (caspase-1, IL-1β and IL-18) in semen of patients presenting for an infertility workup. Further investigation of the inflammasome in various etiologies of male infertility may result in therapeutic interventions. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e909 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Emad Ibrahim More articles by this author Karen Ibrahim More articles by this author Michael Jurewicz More articles by this author Teodoro Aballa More articles by this author George Attia More articles by this author Charles Lynne More articles by this author Nancy Brackett More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Caspase 1: A Novel Serum Marker of Myocardial Remodeling

Purpose Inflammation appears to play a central role in promoting myocardial demise among advanced heart failure (HF) patients (pts). Caspase 1 (C1), a key element of the inflammasome, triggers inflammation, cell death, and progressive remodeling of the heart. Thus, we analyzed C1 expression in normals, end-stage HF pts awaiting ventricular assist device or heart transplant (VAD/TX), and acutely decompensated (AD) HF pts not requiring VAD/TX. We hypothesize a surge of C1 correlates with HF severity and unloading the heart will result in clinical improvement and C1 mitigation. Methods and Materials C1 was measured in the heart muscle and blood of pts pre and post treatment with ELISA: cardiogenic shock (n=45), decompensated HF (n=45), and normal controls (n=5). Additional variables collected include NYHA class, serum brain natriuretic peptide (BNP), and weight. Results In 45 HF pts who underwent VAD/TX, C1 concentrations were four times elevated in the heart compared to normal (p=.02). After VAD therapy (n=21) serum levels of C1 decreased significantly (174±22.7 to 120±14.1 pg/ml, p=.003) while clinical parameters notably improved (BNP 1773±254 to 636±125 pg/ml, p=.003, NYHA class IV to II). Pre-VAD C1 expression in serum highly correlated with C1 expression in heart muscle (R=.54, p=.01). Among 45 ADHF pts treated medically, C1 levels were 27% lower than cardiogenic shock pts (174±22.7 vs 137±9.2 pg/ml, p=.10) and significantly decreased during treatment (137±9.2 to 115±7.8 pg/ml, p=.0006). This was associated with a significant decline in weight and BNP levels (207±11.1 to 205±11 lbs, p=.0003; 1401±200 to 1251±184 pg/ml, p=.004). Conclusions C1 levels assessed in blood or heart muscle appear to mirror the clinical and cellular demise of advanced HF. Unloading of the heart via VAD or medical therapy leads to clinical improvement and marked C1 receding suggesting C1 demarcates reverse remodeling of the myocardium. C1 levels ≤115 pg/ml might be indicative of stable HF.

Involvement of the inflammasome in abnormal semen quality of men with spinal cord injury

To study the mechanism leading to elevated semen cytokines in men with spinal cord injury (SCI) and to understand if inflammasome pathways are involved in this process. To investigate inflammasome components and end-product cytokines in semen of SCI and control subjects. Prospective study. Major university medical center. Men with and without SCI (n = 28 per group). None. Seminal plasma concentrations of caspase-1, interleukin (IL) 1β, and IL-18 were quantified by ELISA. Caspase-1 in sperm fractions and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) in seminal plasma and sperm fractions were identified by Western blot. Localization of proteins in sperm was accomplished by immunocytochemistry. ASC, caspase-1, IL-1β, and IL-18 concentrations were elevated in the seminal plasma of SCI subjects compared with control subjects. ASC and caspase-1 were elevated in sperm cells of SCI subjects. Immunocytochemistry revealed that ASC was located in the acrosome, equatorial segment, and midpiece, and caspase-1 in the midpiece. This study provides the first evidence of ASC in human semen and demonstrates the involvement of inflammasome proteins in semen of men with SCI. These findings suggest an immunologic basis for abnormal semen quality in men with SCI.

2090 POSSIBLE ROLE OF THE INFLAMMASOME IN ABNORMAL SEMEN QUALITY OF MEN WITH SPINAL CORD INJURY

You have accessJournal of UrologyInfertility: Physiology, Pathophysiology, Basic Research1 Apr 20122090 POSSIBLE ROLE OF THE INFLAMMASOME IN ABNORMAL SEMEN QUALITY OF MEN WITH SPINAL CORD INJURY Emad Ibrahim, Xianyang Zhang, Teodoro Aballa, Juan Pablo De Rivero Vaccari, Robert Keane, W. Dalton Dietrich, Charles Lynne, and Nancy Brackett Emad IbrahimEmad Ibrahim Miami, FL More articles by this author , Xianyang ZhangXianyang Zhang Miami, FL More articles by this author , Teodoro AballaTeodoro Aballa Miami, FL More articles by this author , Juan Pablo De Rivero VaccariJuan Pablo De Rivero Vaccari Miami, FL More articles by this author , Robert KeaneRobert Keane Miami, FL More articles by this author , W. Dalton DietrichW. Dalton Dietrich Miami, FL More articles by this author , Charles LynneCharles Lynne Miami, FL More articles by this author , and Nancy BrackettNancy Brackett Miami, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2257AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Most men with spinal cord injury (SCI) have normal sperm concentrations but abnormally low sperm motility. Elevated semen concentrations of inflammatory cytokines contribute to this problem. The mechanism leading to elevated semen cytokines in men with SCI is unknown. To understand if inflammasome pathways are part of the mechanism leading to elevated semen cytokines in men with SCI, this study investigated inflammasome complex proteins and end product cytokines in semen of SCI and control subjects. METHODS Semen samples were collected from 37 men with SCI and 39 healthy non-SCI men as control subjects. Penile vibratory stimulation and electroejaculation were utilized to collect semen samples from men with SCI. Control subjects collected semen by masturbation. Semen was divided into two aliquots. One aliquot was centrifuged to obtain seminal plasma (the supernatant). The other aliquot was processed on a density gradient to isolate sperm cells. Western blot analysis was used to detect concentrations of caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC), while immunocytochemistry with confocal microscopy localized these proteins on the sperm cell. Concentrations of caspase-1, IL-1β and IL-18 in the seminal plasma were determined by ELISA. RESULTS Concentrations of the following were elevated in the seminal plasma of SCI subjects compared to control subjects: caspase-1 (1187.0 ± 220.1 vs. 190.2 ± 39.0 pg/ml, p ≤ 0.0001); ASC (0.9792 ± 0.1340 vs. 0.1155 ± 0.0333 relative intensity, p ≤ 0.0001); IL-1β (92.6 ± 19.9 vs. 15.0 ± 4.1 pg/ml, p ≤ 0.0003); and IL-18 (2045.0 ± 729.1 vs. 64.9 ± 18.8 pg/ml, p ≤ 0.0087). Statistical analysis showed a positive correlation between the levels of caspase-1 and ASC in the seminal plasma (n=61, r2 = 0.42, p < 0.0001) and a negative correlation between sperm motility and the levels of ASC in the seminal plasma (n=62, r2 = 0.29, p < 0.0001). When examining sperm cell extracts by Western blot, ASC and caspase-1 were found to be elevated in SCI subjects compared to controls. The expression of these two proteins was further confirmed by immunocytochemistry with confocal microscopy. Caspase-1 was located in the head and the midpiece whereas ASC was located mainly in the proximal section of the sperm tail. CONCLUSIONS This study provides the first evidence of the inflammasome in human semen. The involvement of caspase-1 and ASC suggests an immunologic basis for abnormal semen quality in men with SCI. Inflammasome inactivation may be a possible target for therapeutic intervention. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e842-e843 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Emad Ibrahim Miami, FL More articles by this author Xianyang Zhang Miami, FL More articles by this author Teodoro Aballa Miami, FL More articles by this author Juan Pablo De Rivero Vaccari Miami, FL More articles by this author Robert Keane Miami, FL More articles by this author W. Dalton Dietrich Miami, FL More articles by this author Charles Lynne Miami, FL More articles by this author Nancy Brackett Miami, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Caspase-1 Promiscuity Is Counterbalanced by Rapid Inactivation of Processed Enzyme

Members of the caspase family of cysteine proteases coordinate the highly disparate processes of apoptosis and inflammation. However, although hundreds of substrates for the apoptosis effector caspases (caspase-3 and caspase-7) have been identified, only two confirmed substrates for the key inflammatory protease (caspase-1) are known. Whether this reflects intrinsic differences in the substrate specificity of inflammatory versus apoptotic caspases or their relative abundance in vivo is unknown. To address this issue, we have compared the specificity of caspases-1, -3, and -7 toward peptide and protein substrates. Contrary to expectation, caspase-1 displayed concentration-dependent promiscuity toward a variety of substrates, suggesting that caspase-1 specificity is maintained by restricting its abundance. Although endogenous concentrations of caspase-1 were found to be similar to caspase-3, processed caspase-1 was found to be much more labile, with a half-life of ∼9 min. This contrasted sharply with the active forms of caspase-3 and caspase-7, which exhibited half-lives of 8 and 11 h, respectively. We propose that the high degree of substrate specificity displayed by caspase-1 is maintained through rapid spontaneous inactivation of this protease.

Evidence of the involvement of caspase-1 under physiologic and pathologic cellular stress during human pregnancy: A link between the inflammasome and parturition

Objective. Caspase-1 is a component of the NALP3 inflammasome, a cytosolic multiprotein complex that mediates the processing of pro-inflammatory caspases and cytokines. The inflammasome represents the first line of defense against cellular stress and is a crucial component of innate immunity. Caspase-1 is the enzyme responsible for the cleavage and activation of interleukin (IL)-1β, which is a potent pro-inflammatory cytokine, and plays a central role in the mechanisms leading to labor (preterm and term) particularly in the context of intrauterine infection/inflammation. In addition, caspase-1 cleaves IL-18 and IL-33. The objectives of this study were to determine whether there is a relationship between amniotic fluid concentrations of caspase-1 and gestational age, parturition (term and preterm), and intra-amniotic infection/inflammation (IAI).Study design. A cross-sectional study was conducted including 143 pregnant women in the following groups: (1) mid-trimester of pregnancy (n = 18); (2) term not in labor (n = 25); (3) term in labor (n = 28); (4) preterm labor (PTL) who delivered at term (n = 23); (5) PTL without IAI who delivered preterm (n = 32); (6) PTL with IAI who delivered preterm neonates (n = 17). Caspase-1 concentrations in amniotic fluid were determined by a specific and sensitive immunoassay. Non-parametric statistics were used for analysis.Results. (1) Caspase-1 was detected in amniotic fluid of women at term, but in none of the mid-trimester samples. (2) Patients in labor at term had a significantly higher median amniotic fluid concentration of caspase-1 than women at term not in labor (term in labor: 10.5 pg/mL, range 0.0–666.0 vs. term not in labor: 5.99 pg/mL, range 0.0–237.4; p < 0.05). (3) Among patients with spontaneous PTL, those with IAI (median 41.4 pg/mL, range 0.0–515.0) had a significantly higher median amniotic fluid caspase-1 concentration than those without IAI who delivered preterm (median 0.0 pg/mL, range 0.0–78.4) and than those who delivered at term (median 0.0 pg/mL, range 0.0–199.5); p < 0.001 for both comparisons.Conclusions. (1) The presence and concentration of caspase-1 in the amniotic fluid varies as a function of gestational age. (2) Women with spontaneous labor at term had a higher median caspase-1 amniotic fluid concentration than women at term without labor. This suggests that the inflammasome may be activated in spontaneous parturition at term. Since most women with labor do not have intra-amniotic infection, we propose that cellular stress during labor accounts for activation of the inflammasome. (3) Preterm labor associated with infection/inflammation was also associated with a high concentration of caspase-1, suggesting that infection may induce caspase-1 production and activation of the inflammasome. (4) The sequential activation of the inflammasome and caspase-1, leading to interleukin-1β processing and secretion, is a candidate pathway leading to the activation of the common pathway of parturition.

SCD30, interleukin-1β-converting enzyme and anti-Annexin V autoantibodies concentrations in heart transplant recipients

sCD30 and ICE/caspase-1 as apoptosis-regulating factors are suspected to be involved in the survival rate of immunocompetent cells during immunosuppression after allotransplantation. Serum CD30 and ICE/caspase-1 concentrations were estimated and associated with unspecific serum apoptosis marker – anti-Annexin V antibodies and myocardial biopsies results. Materials and methods 28 clinically stabile patients – heart transplant recipients at least 3 months after cardiac transplantation performed due to heart failure caused by ischaemic and/or congestive cardiomyopathy or/and primary valvular heart disease (26 men and 2 women, mean age = 36.8 years, S.D. = 7.6) with normal heart function assessed by use of ultrasound scan – were involved into trial. The patients were divided and analyzed in two ways: first according to the results of elective endomyocardial biopsies and second to main immunosuppressive agent used. The enzyme immunoassay (CD30, Dako; interleukin-1β-converting enzyme (ICE)/Caspase-1 ELISA and anti-Annexin V BENDER MedSystem) for soluble CD30, caspase-1 and anti-Annexin V autoantibodies serum levels was used. Results sCD30 and caspase-1 concentrations were non-significantly up-regulated in all analysed groups – with or without rejection signs or immunosuppressed with cyclosporine or especially tacrolimus. In contrast anti-Annexin V autoantibodies concentration was non-significantly down-regulated also in all studied groups. Moreover in the group with signs of transplant rejection, strong negative correlation between anti-Annexin antibodies and rejection grade was observed (− 0.65, p < 0.05). Biopsy results were comparable in groups treated with tacrolimus and cyclosporine A. Conclusions The increasing tendency of sCD30 and caspase-1 as well as the decrease in anti-Annexin V autoantibodies concentrations in heart recipients could be the result of post-transplant apoptosis disturbances. This tendency seems to be inhibited in a greater degree by tacrolimus than by cyclosporine. Anti-Annexin V autoantibodies might be considered as negative rejection markers due to their strong negative correlation with the rejection grade.