CXCL14 preferentially synergizes with homeostatic chemokine receptor systems

Reflecting their importance in immunity, the activity of chemokines is regulated on several levels, including tissue and context-specific expression and availability of their cognate receptor on target cells. Chemokine synergism, affecting both chemokine and chemokine receptor function, has emerged as an additional control mechanism. We previously demonstrated that CXCL14 is a positive allosteric modulator of CXCR4 in its ability to synergize with CXCL12 in diverse cellular responses. Here, we have extended our study to additional homeostatic, as well as a selection of inflammatory chemokine systems. We report that CXCL14 strongly synergizes with low (sub-active) concentrations of CXCL13 and CCL19/CCL21 in in vitro chemotaxis with immune cells expressing the corresponding receptors CXCR5 and CCR7, respectively. CXCL14 by itself was inactive, not only on cells expressing CXCR5 or CCR7 but also on cells expressing any other known conventional or atypical chemokine receptor, as assessed by chemotaxis and/or β-arrestin recruitment assays. Furthermore, synergistic migration responses between CXCL14 and inflammatory chemokines CXCL10/CXCL11 and CCL5, targeting CXCR3 and CCR5, respectively, were marginal and occasional synergistic Ca2+ flux responses were observed. CXCL14 bound to 300-19 cells and interfered with CCL19 binding to CCR7-expressing cells, suggesting that these cellular interactions contributed to the reported CXCL14-mediated synergistic activities. We propose a model whereby tissue-expressed CXCL14 contributes to cell localization under steady-state conditions at sites with prominent expression of homeostatic chemokines.publishe

Prefrontal cortex oxygenation during endurance performance: A systematic review of functional near-infrared spectroscopy studies.

A myriad of factors underlie pacing-/exhaustion-decisions that are made during whole-body endurance performance. The prefrontal cortex (PFC) is a brain region that is crucial for decision-making, planning, and attention. PFC oxygenation seems to be a mediating factor of performance decisions during endurance performance. Nowadays, there is no general overview summarizing the current knowledge on how PFC oxygenation evolves during whole-body endurance performance and whether this is a determining factor. Three electronic databases were searched for studies related to the assessment of PFC oxygenation, through near-IR spectroscopy (NIRS), during endurance exercise. To express PFC oxygenation, oxygenated (HbO ) and deoxygenated hemoglobin (HHb) concentrations were the primary outcome measures. Twenty-eight articles were included. Ten articles focused on assessing prefrontal oxygenation through a maximal incremental test (MIT) and 18 focused on using endurance tasks at workloads ranging from low intensity to supramaximal intensity. In four MIT studies measuring HbO , an increase of HbO was noticed at the respiratory compensation point (RCP), after which it decreased. HbO reached a steady state in the four studies and increased in one study until exhaustion. All studies found a decrease or steady state in HHb from the start until RCP and an increase to exhaustion. In regard to (non-incremental) endurance tasks, a general increase in PFC oxygenation was found while achieving a steady state at vigorous intensities. PCF deoxygenation was evident for near-to-maximal intensities at which an increase in oxygenation and the maintenance of a steady state could not be retained. : MIT studies show the presence of a cerebral oxygenation threshold (ThCox) at RCP. PFC oxygenation increases until the RCP threshold, thereafter, a steady state is reached and HbO declines. This study shows that the results obtained from MIT are transferable to non-incremental endurance exercise. HbO increases during low-intensity and moderate-intensity until vigorous-intensity exercise, and it reaches a steady state in vigorous-intensity exercise. Furthermore, ThCox can be found between vigorous and near-maximal intensities. During endurance exercise at near-maximal intensities, PFC oxygenation increases until the value exceeding this threshold, resulting in a decrease in PFC oxygenation. Future research should aim at maintaining and improving PFC oxygenation to help in improving endurance performance and to examine whether PFC oxygenation has a role in other performance-limiting factors. [Abstract copyright: Copyright © 2021 De Wachter, Proost, Habay, Verstraelen, Díaz-García, Hurst, Meeusen, Van Cutsem and Roelands.

Cloning, constitutive activity and expression profiling of two receptors related to relaxin receptors in Drosophila melanogaster

Leucine-rich repeat containing G protein-coupled receptors (LGRs) comprise a cluster of transmembrane proteins, characterized by the presence of a large N-terminal extracellular domain. This receptor group can be classified into three subtypes. Belonging to the subtype C LGRs are the mammalian relaxin receptors LGR7 (RXFP1) and LGR8 (RXFP2), which mediate important reproductive and other processes. We identified two related receptors in the genome of the fruit fly and cloned their open reading frames into an expression vector. Interestingly, dLGR3 demonstrated constitutive activity at very low doses of transfected plasmid, whereas dLGR4 did not show any basal activity. Both receptors exhibited a similar expression pattern during development, with relatively high transcript levels during the first larval stage. In addition, both receptors displayed higher expression in male adult flies as compared to female flies. Analysis of the tissue distribution of both receptor transcripts revealed a high expression of dLGR3 in the female fat body, while the expression of dLGR4 peaked in the midgut of both the wandering and adult stage.publisher: Elsevier articletitle: Cloning, constitutive activity and expression profiling of two receptors related to relaxin receptors in Drosophila melanogaster journaltitle: Peptides articlelink: http://dx.doi.org/10.1016/j.peptides.2014.07.014 content_type: article copyright: Copyright © 2014 Elsevier Inc. All rights reserved.status: publishe

Human Chemokines as Antimicrobial Peptides with Direct Parasiticidal Effect on Leishmania mexicana In Vitro

Chemokines and chemokine receptor-mediated effects are important mediators of the immunological response and cure in human leishmaniasis. However, in addition to their signalling properties for leukocytes, many chemokines have also been shown to act directly as antimicrobial peptides on bacteria and fungi. We screened ten human chemokines (CXCL2, CXCL6, CXCL8, CXCL9, CXCL10, CCL2, CCL3, CCL20, CCL27, CCL28) for antimicrobial effects on the promastigote form of the protozoan parasite Leishmania mexicana, and observed direct parasiticidal effects of several, CCL28 being the most potent. Damage to the plasma membrane integrity could be visualised by entrance of propidium iodide, as measured with flow cytometry, and by scanning electron microscopy, which showed morphological changes and aggregation of cells. The findings were in concordance with parasiticidal activity, measured by decreased mitochondrial activity in an MTT-assay. This is the first report of direct antimicrobial activity by chemokines on parasites. This component of immunity against Leishmania parasites identified here warrants further investigation that might lead to new insight in the mechanisms of human infection and/or new therapeutic approaches

Does Mental Fatigue Negatively Affect Outcomes of Functional Performance Tests?

Purpose Mental fatigue impairs psychomotor skill performance by affecting visuomotor reaction time, accuracy, and decision-making. Recently, neurocognitive functional performance tests (FPT) that integrate these outcomes have been developed. The aim of this study was to assess the effect of mental fatigue on traditional and neurocognitive FPT in healthy adults. Methods Fourteen volunteers (four women; mean ± SD age, 22 ± 1 yr; height, 176.9 ± 8.4 cm; weight, 69.7 ± 10.4 kg) participated in a randomized counterbalanced crossover design. A 100% incongruent Stroop color word test of 90 min was used to induce mental fatigue and the control task encompassed watching a 90-min documentary. Traditional FPT comprised a single-leg hop for distance, countermovement jump, and Y-balance test, whereas the neurocognitive FPT encompassed the reactive balance test (RBT). All FPTs were evaluated pre-post the 90-min task. Mental fatigue was assessed using the Stroop task, visual analog scale for mental fatigue, and the Eriksen-Flanker task. Results Mental fatigue was successfully induced, as shown by a significant increase in visual analog scale for mental fatigue (P < 0.001), with no decrease in performance on the Stroop and Eriksen-Flanker task. No interaction effect of mental fatigue was found for the Y-balance test, single-leg hop, and countermovement jump. For the RBT accuracy, a significant interaction effect of mental fatigue and time was observed (P = 0.024), with participants performing significantly worse when mentally fatigued. No interaction effect or main effect of condition and time was observed when considering the effect of mental fatigue on visuomotor reaction time in the RBT. Conclusions Mental fatigue negatively affects a neurocognitive FPT, indicated by a decreased accuracy in response to visual stimuli in the RBT. Traditional FPT remained unaffected by mental fatigue

Correction: Habay et al. Mental Fatigue-Associated Decrease in Table Tennis Performance: Is There an Electrophysiological Signature? Int. J. Environ. Res. Public Health 2021, 18, 12906

In the published publication [...

Does Acute Fatigue Negatively Affect Intrinsic Risk Factors of the Lower Extremity Injury Risk Profile? A Systematic and Critical Review

Background: Acute fatigue is hypothesized to alter lower extremity injury risk profiles by affecting intrinsic risk factors (i.e. single leg postural control, hamstring strength). However, no systematic overview exists that merges the insights into prospective lower extremity injury risk profiling with the effect of acute fatigue on functional test performance. Objective: The objective of this review is to identify the influence of acute fatigue on prospectively determined modifiable intrinsic risk factors for lower extremity injuries. Design: Systematic review. Methods: PubMed (MEDLINE), Web of Science, PEDro, and Cochrane Library were searched until 29 May 2019. Studies were eligible when the study outcomes encompassed intrinsic modifiable risk factors for lower extremity injury, an acute fatigue intervention, and included healthy athletes or physically active people. Intrinsic modifiable risk factors were identified through recent systematic reviews and meta-analyses, and the referenced original research papers were used to determine outcome measures associated with increased injury risk. Results: Forty-three studies reported acute fatigue effects on modifiable risk factors, with eight studies matching all criteria for data-extraction. Acute fatigue can decrease single leg postural control, decrease ankle joint position sense, decrease isokinetic strength of hamstring and quadriceps muscles and can affect isokinetic hamstring:quadriceps ratios. Conclusion: Acute fatigue affects prospective intrinsic modifiable risk factors for lower extremity injury, indicating an altered injury risk profile for lateral ankle sprain, patellofemoral pain syndrome and hamstring injuries. Future research should allow for individual fatiguability as a relevant outcome, and merge insights from athlete-centred injury risk profiling and fatigue

The chemokine receptor CXCR7 is expressed on lymphatic endothelial cells during renal allograft rejection

CXCR7 is an atypical receptor for the chemokines CXCL11 and CXCL12, which were found to be involved in animal models of allograft injury. We studied the expression of CXCR7 and its ligands in human kidneys by first quantifying the mRNA in 53 renal allograft biopsies. Receptor and ligand mRNAs were expressed in renal allografts, with a significant induction of CXCL11 and CXCL12 in biopsies showing borderline lesions and acute rejection. Immunohistochemical analysis for CXCR7 was performed in a series of 64 indication and 24 protocol biopsies. The indication biopsies included 46 acute rejections, 6 with interstitial fibrosis and tubular atrophy, and 12 pretransplant biopsies as controls. In control biopsies, CXCR7 protein was found on smooth muscle and on endothelial cells of a small number of peritubular vessels. The number of CXCR7-positive vessels was increased in acute rejection and, using double immunofluorescence labeling, a subset of these CXCR7-positive endothelial cells were identified as lymphatic vessels. Both CXCR7-positive blood and lymphatic vessels increased during allograft rejection. We found that CXCR7 is present in both blood and lymphatic endothelial cells in human renal allografts. Whether its presence modulates the formation of chemokine gradients and the recruitment of inflammatory cells will require further experimental studies

Lipopolysaccharide exposure modifies high tidal volume ventilation-induced proinflammatory mediator expression in newborn rat lungs

Infection/inflammation and mechanical ventilation have both independently been shown to increase cytokine/chemokine levels in lung tissue and blood samples of premature patients. Little is known about the combined effect of systemic inflammation and mechanical ventilation on cytokine expression in the lung. We tested whether pre-existing inflammation induced by lipopolysaccharide (LPS) exposure would modify cytokine/chemokine response in newborn rat lungs to high tidal volume ventilation (HTVV). Newborn rats were randomly assigned to four groups: groups I and II (saline); groups III and IV: 3 mg/kg LPS. Groups II and IV were 24h later subjected to 3h of ventilation with a tidal volume of 25 mL/kg. HTVV alone increased IL-1beta, IL-6 and the chemokine (C-X-C motif) ligand 2 (CXCL2) mRNA expression. Although the cytokine response to LPS alone had disappeared after 24 h, the combination of LPS pretreatment and HTVV significantly increased the expression of IL-6 and IL-1beta mRNA when compared with HTVV alone. TNF-alpha expression was increased neither by HTVV alone nor in combination with LPS. IL-6 protein content in bronchoalveolar lavage increased due to the combined treatment. Thus, a subtle pre-existing inflammation combined with HTVV amplifies the proinflammatory cytokine/chemokine expression in the newborn rat lung compared with HTVV alone