Testosterone Inhibits Secretion of the Pro-Inflammatory Chemokine CXCL1 from Astrocytes.

Astrocytes play an important role in the regulation of the inflammatory response in the CNS, e.g., in demyelinating diseases. Since the chemokine CXCL1 is known to be secreted by astrocytes and to have a pro-inflammatory effect on immune cells in the CNS, we verified the effect of testosterone on its secretion in vitro (in the astrocytic cell line DI TNC1). Testosterone reduced the increase in CXCL1 production caused by the pro-inflammatory agent lysophosphatidylcholine and restored the basal production level of CXCL1. The androgen receptor (present and functional in the studied cell line) was strongly suggested to mediate this effect-its non-steroid ligand flutamide exerted an agonist-like effect, mimicking the activity of testosterone itself on CXCL1 secretion. This novel mechanism has important implications for the known immunomodulatory effect of testosterone and potentially other androgenic hormones. It provides a potential explanation on the molecular level and shows that astrocytes are important players in inflammatory homeostasis in the CNS and its hormonal regulation. Therefore, it suggests new directions for the development of the therapeutic intervention.

An Overview of Multiple Sclerosis In Vitro Models.

Multiple sclerosis (MS) still poses a challenge in terms of complex etiology, not fully effective methods of treatment, and lack of healing agents. This neurodegenerative condition considerably affects the comfort of life by causing difficulties with movement and worsening cognition. Neuron, astrocyte, microglia, and oligodendrocyte activity is engaged in multiple pathogenic processes associated with MS. These cells are also utilized in creating in vitro cellular models for investigations focusing on MS. In this article, we present and discuss a summary of different in vitro models useful for MS research and describe their development. We discuss cellular models derived from animals or humans and present in the form of primary cell lines or immortalized cell lines. In addition, we characterize cell cultures developed from induced pluripotent stem cells (iPSCs). Culture conditions (2D and 3D cultures) are also discussed.

CXCL1 as a Potential Biomarker of Plaque Instability in Carotid Stenosis. Preliminary Report.

Biomarkers of atherosclerotic plaque instability are needed. This study aimed to evaluate the level of chemokine CXCL1 (CXC motif ligand 1) in plasma and atherosclerotic plaques in patients with carotid stenosis and correlate that with plaque morphology. The study group included 82 patients (30 women and 52 men) aged 50-90 years (mean 68.1 ± 8.9) who underwent elective carotid endarterectomy. The obtained atherosclerotic plaques were macroscopically and microscopically assessed according to the American Heart Association (AHA) classification. Fifty-one (62.2%) and 31 (37.8%) of the plaques were unstable and stable, respectively. The mean concertation of CXCL1 in plaques in asymptomatic and symptomatic patients was 0.00 (±0.00) vs 88.90 (±95.19) pg/ml, respectively (P = 0.000). The mean plasma concentration of CXCL1 in the study group was 42.40 (±85.79) pg/ml, while in the control group (healthy volunteers without lesions in the carotid arteries) it was 0.00 pg/mL (±0.00) (P = 0.000). The mean plasma CXCL1 concertation in asymptomatic and symptomatic patients was 22.08 (±49.13) versus 67.72 (±107.91) pg/ml, respectively (P = 0.031). Significantly higher CXCL1 concentration in atherosclerotic plaques and plasma in symptomatic patients compared with asymptomatic patients probably resulted from unstable lesions in the carotid arteries.

The Role of Neutrophils in Multiple Sclerosis and Ischemic Stroke.

Inflammation plays an important role in numerous central nervous system (CNS) disorders. Its role is ambiguous-it can induce detrimental effects, as well as repair and recovery. In response to injury or infection, resident CNS cells secrete numerous factors that alter blood-brain barrier (BBB) function and recruit immune cells into the brain, like neutrophils. Their role in the pathophysiology of CNS diseases, like multiple sclerosis (MS) and stroke, is highly recognized. Neutrophils alter BBB permeability and attract other immune cells into the CNS. Previously, neutrophils were considered a homogenous population. Nowadays, it is known that various subtypes of these cells exist, which reveal proinflammatory or immunosuppressive functions. The primary goal of this review was to discuss the current knowledge regarding the important role of neutrophils in MS and stroke development and progression. As the pathogenesis of these two disorders is completely different, it gives the opportunity to get insight into diverse mechanisms of neutrophil involvement in brain pathology. Our understanding of the role of neutrophils in CNS diseases is still evolving as new aspects of their activity are being unraveled. Neutrophil plasticity adds another level to their functional complexity and their importance for CNS pathophysiology.