Jan Kochanowski

Fractalkine (CX3CL1) and Its Receptor CX3CR1 May Contribute to Increased Angiogenesis in Diabetic Placenta

Chemokine CX3CL1 is unique, possessing the ability to act as a dual agent: chemoattractant and adhesive compound. Acting via its sole receptor CX3CR1, CX3CL1 participates in many processes in human placental tissue, including inflammation and angiogenesis. Strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokines secretion, CX3CL1 may act locally as a key angiogenic factor. Both clinical observations and histopathological studies of the diabetic placenta have confirmed an increased incidence of hypoxia and inflammatory reactions with defective angiogenesis. In this study we examined comparatively (diabetes class C complicated versus normal pregnancy) the correlation between CX3CL1 content in placental tissue, the mean CX3CR1 expression, and density of the network of placental microvessels. A sandwich enzyme immunoassay was applied for CX3CL1 measurement in placental tissue homogenates, whereas quantitative immunohistochemical techniques were used for the assessment of CX3CR1 expression and the microvascular density. Significant differences have been observed for all analyzed parameters between the groups. The mean concentration of CX3CL1 in diabetes was increased and accompanied by augmented placental microvessel density as well as a higher expression of CX3CR1. In conclusion, we suggest involvement of CX3CL1/CX3CR1 signaling pathway in the pathomechanism of placental microvasculature remodeling in diabetes class C.

Chorioamnionitis (ChA) modifies CX3CL1 (fractalkine) production by human amniotic epithelial cells (HAEC) under normoxic and hypoxic conditions

BackgroundChemokine CX3CL1 possesses unique properties, including combined adhesive and chemotactic functions. Human amniotic epithelial cells (HAEC) show expression of CX3CL1 receptor (CX3CR1) and produce CX3CL1 in response to both physiologic and pathologic stimuli. Chorioamnionitis (ChA) is a common complication of pregnancy and labour. ChA is often accompanied by local hypoxia because of the high oxygen consumption at the site of inflammation. We examined comparatively (ChA-complicated vs. normal pregnancy) CX3CR1 expression and the effects of hypoxia, lipopolysaccharide (LPS), and CX3CR1 blockade on CX3CL1 production in HAEC cultured in vitro.MethodsHAEC have been isolated using trypsinization, and cultured under normoxia (20% O2) vs. hypoxia (5% O2). According to the experimental design, LPS (1 μg/ml) and neutralizing anti-CX3CR1 antibodies were added at respective time points. Mean CX3CL1 concentration in the supernatant samples were determined by ELISA. Expression of immunostained CX3CR1 was analyzed using quantitative morphometry.ResultsWe have found that the mean levels of CX3CL1 and CX3CR1 expression were remarkably (p < 0.05) higher in ChA, compared to normal pregnancy. Significantly increased expression of CX3CR1 was observed in ChA during both normoxia and hypoxia. Hypoxia exposure produced decrease in the mean concentration of CX3CL1 in both groups, however this reduction was stronger in normal pregnancy. In normoxia, LPS-evoked rise in the mean concentration of CX3CL1 was higher (p < 0.05) in normal pregnancy. This response was positively correlated with CX3CR1 expression. Blockade of CX3CR1 canceled the secretory response to LPS in all groups.ConclusionsChA-complicated pregnancy up-regulates CX3CR1 in HAEC cultured in vitro with simultaneous increase in CX3CL1 production. Hypoxia-resistant production of CX3CL1 may be responsible for ChA-related complications of pregnancy and labor.

Adipokine profile in patients with anorexia nervosa

INTRODUCTION Anorexia nervosa (AN) is an eating disorder characterised with extremely low weight. Adipokines are adipose tissue-derived substances that show a wide spectrum of biological activities. We aimed to assess selected adipokine levels in women with AN before and after nutritional intervention. We also sought to examine whether BMI is the only confounding factor influencing adipokine assessment in AN. MATERIAL AND METHODS Sixty-five women participated in the study: 20 individuals with AN before any treatment, 18 AN patients after nutritional intervention lasting for at least six months, and 27 women as controls. In all participants blood collection and anthropometric measurements were performed. ELISA was used for evaluation of leptin receptor, adiponectin and its isoforms, and resistin. Leptin was assessed with RIA, and visfatin was measured with EIA assay. RESULTS Leptin and free leptin index (FLI) were lowest in treatment-naïve AN women. HMW-adiponectin and visfatin were enhanced in AN. Other adipokine levels showed no significant differences. When two subsets of anorexia nervosa were compared, only leptin, leptin receptor, and FLI were markedly different. When data were adjusted to BMI, leptin and FLI remained significantly different in the pre-treated AN subgroup when compared with the control group. CONCLUSIONS Our results suggest that leptin is the most important adipokine in AN. It is also important that in our AN population leptin and FLI are the only factors that are influenced not only by the fat content.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) in humans with multiple sclerosis.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system that leads to demyelination and neurodegeneration. VIP and PACAP are structurally related neuropeptides with neuroprotective and anti-inflammatory activities. To evaluate VIP and PACAP-38 in plasma and CSF in humans in correlation with IL-6, IL-10 and TNFα, we compared 20 MS individuals with 27 healthy controls. In MS, a decrease in PACAP-38 in CSF and a decrease in plasma IL-6 concentration were seen. A positive correlation between plasma VIP and plasma IL-6 was identified. We conclude that VIP and PACAP may influence the course of MS.