scholarly journals The sympathetic nervous system stimulates anti-inflammatory B cells in collagen-type II-induced arthritis

2011 ◽  
Vol 71 (3) ◽  
pp. 432-439 ◽  
Author(s):  
Georg Pongratz ◽  
Madlen Melzer ◽  
Rainer H Straub
Keyword(s):  
Nervous System ◽  
B Cells ◽  
Sympathetic Nervous System ◽  
B Cell ◽  
Late Phase ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Sympathetic Nervous ◽  
Anti Inflammatory

BackgroundAs previously shown, the sympathetic nervous system (SNS) shows proinflammatory activity during initiation of arthritis but is anti-inflammatory in established collagen-induced arthritis (CIA). Interleukin 10 (IL-10)-producing B cells suppress arthritis and are a potential target of the SNS because (1) B cells express functional β2-adrenoceptors (β2ARs) and (2) IL-10, at least in monocytes/macrophages, is regulated in a cAMP/PKA/CREB-dependent manner.ObjectiveTo test the hypothesis that anti-inflammatory effects of the SNS in CIA are mediated by stimulating IL-10-producing anti-inflammatory B cells.MethodsCollagen-induced arthritis in DBA/1 mice, sympathectomy, adoptive B cell transfer, in vitro B cell culture, and assessment of B cell IL-10 production.Results and conclusionMice treated with B cells from SNS-intact mice showed less severe arthritis than mice treated with B cells from sympathectomised mice. This anti-inflammatory action of B cells from SNS-intact mice correlated with increased IL-10 produced by B cells, which was mediated by norepinephrine (NE), in a β2AR, PKA-dependent manner. However, an NE-mediated increase in IL-10 was seen only in B cells from immunised but not naive mice, explaining in part the anti-inflammatory properties of the SNS in the late phase of arthritis. Finally, animals treated with B cells isolated from immunised mice and activated in vitro in the presence of a β2AR stimulus showed a decrease in arthritis severity in comparison with controls, an approach that might be used for future cellular treatment strategies.

scholarly journals TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines

2020 ◽  
Author(s):  
Nadine Honke ◽  
Torsten Lowin ◽  
Birgit Opgenoorth ◽  
Namir Shaabani ◽  
Alexander Lautwein ◽  
...  
Keyword(s):  
Nervous System ◽  
B Cells ◽  
Sympathetic Nervous System ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Adrenergic Receptors ◽  
Regulatory Function ◽  
Immune Balance ◽  
Sympathetic Nervous ◽  
Anti Inflammatory

AbstractThe sympathetic nervous system (SNS) contributes to immune balance by promoting anti-inflammatory B cells. However, whether B cells possess a self-regulating mechanism by which they modulate regulatory B cell (Breg) function is not well understood. In this study, we investigated the ability of B cells to synthesize catecholamines upon stimulation with different B cell activators. We found, that expression of the enzymes required to generate catecholamines, is upregulated by TLR9. TLR-9-specific expression of tyrosine hydroxylase (TH) correlated with upregulation of adrenergic receptors, enhanced IL-10 production, and with an overexpression of the co-inhibitory ligands PD-L1 and FasL. Moreover, concomitant stimulation of ß1-3-adrenergic receptors together with a BCR/TLR9 stimulus enhances the anti-inflammatory potential of Bregs to suppress CD4 T cells, a crucial population in the pathogenesis of autoimmune diseases, like rheumatoid arthritis. In conclusion, our data show that B cells possess autonomous mechanisms to modulate their regulatory function. These findings help to better understand the function of Bregs in autoimmune diseases and the interplay of sympathetic nervous system and B cell function.

scholarly journals Carnitine Palmitoyltransferase-1 (CPT-1) Activity Stimulation by Cerulenin via Sympathetic Nervous System Activation Overrides Cerulenin’s Peripheral Effect

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3197-3204 ◽  
Author(s):  
Yong-Jun Jin ◽  
Song-Zhe Li ◽  
Zheng-Shan Zhao ◽  
Juan Ji An ◽  
Ryang Yeo Kim ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Core Temperature ◽  
Arcuate Nucleus ◽  
Late Phase ◽  
Ventromedial Hypothalamus ◽  
Sympathetic Nervous ◽  
Carnitine Palmitoyltransferase 1

Abstract To clarify the paradoxic effects of cerulenin, namely its in vitro inhibitory effects on fat catabolism and its in vivo reduction of fat mass, we studied the in vivo and in vitro effects of cerulenin on carnitine palmitoyltransferase-1 (CPT-1) activity, the rate-limiting enzyme of fatty acid oxidation. A single ip injection of cerulenin significantly reduced body weight and increased core temperature without significantly reducing food intake. In situ hybridization study revealed that a single injection of cerulenin did not affect the expression of orexigenic neuropeptide mRNA. Cerulenin’s effect on CPT-1 activity was biphasic in the liver and muscle: early suppression during the first 1 h and late stimulation in the 3–5 h after ip treatment. In vitro cerulenin treatment reduced CPT-1 activity, which was overcome by cotreating with catecholamine. Intracerebroventricular injection of cerulenin increased CPT-1 activity significantly in soleus muscle, and this effect was sustained for up to 3 h. Pretreatment with α-methyl-p-tyrosine inhibited the cerulenin-induced increase in core temperature and the late-phase stimulating effect of cerulenin on CPT-1 activity. In adrenalectomized mice, cerulenin also increased the activity. In vivo cerulenin treatment enhanced muscle CPT-1 activity in monosodium glutamate-treated arcuate nucleus lesioned mice but not in gold thioglucose-treated ventromedial hypothalamus lesioned mice. These findings suggest that cerulenin-induced late-phase stimulating effects on CPT-1 activity and energy expenditure is mediated by the activation of innervated sympathetic nervous system neurons through the firing of undefined neurons of the ventromedial hypothalamus, rather than the arcuate nucleus.

scholarly journals Involvement of Lactate and Pyruvate in the Anti-Inflammatory Effects Exerted by Voluntary Activation of the Sympathetic Nervous System

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 148 ◽  
Author(s):  
Jelle Zwaag ◽  
Rob ter Horst ◽  
Ivana Blaženović ◽  
Daniel Stoessel ◽  
Jacqueline Ratter ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Training Program ◽  
Voluntary Activation ◽  
Cori Cycle ◽  
Breathing Exercises ◽  
Lactate And Pyruvate ◽  
Sympathetic Nervous ◽  
Anti Inflammatory

We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1β and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.

In vitro associative conditioning of Hermissenda: cumulative depolarization of type B photoreceptors and short-term associative behavioral changes

1987 ◽  
Vol 57 (6) ◽  
pp. 1639-1668 ◽  
Author(s):  
J. Farley ◽  
D. L. Alkon
Keyword(s):  
Nervous System ◽  
B Cells ◽  
Hair Cell ◽  
B Cell ◽  
Behavioral Changes ◽  
Type B ◽  
Short Term ◽  
Phototactic Behavior ◽  
Optic Ganglion

Cumulative depolarization of Hermissenda type B photoreceptors, a short-term neural correlate of associative learning, was produced by simulating associative training in the isolated nervous system (in vitro conditioning). This simulation entailed stimulation and recording from three classes of neurons normally affected by the associative training procedure: a type B photoreceptor, the silent/excitatory (S/E) optic ganglion cell, and a statocyst caudal hair cell. Exposure of the isolated nervous system to five simultaneous pairings of light and current-induced impulse activity of the caudal hair cell resulted in an average 10-mV depolarization of type B cells. Cumulative depolarization was found to be pairing specific, to occur with a minimal number of training trials, and was paralleled by short-term pairing-specific changes in phototactic behavior for the intact animal. Two important determinants of cumulative depolarization were found to be the magnitude and duration of the long-lasting depolarization (LLD) response of type B cells to light, and a pairing-specific synaptic facilitation of the LLD response. The synaptic facilitation arose from two distinct sources: increased excitatory postsynaptic potential (EPSP) feedback on B cells following light and caudal hair cell stimulation pairings, and disinhibition of the type B photoreceptor following pairings. The S/E optic ganglion cell was found to be a potent regulator of B cell EPSPs. Cumulative depolarization was substantially reduced when the S/E cell was hyperpolarized throughout the course of pairings. Conversely, pairings of light with depolarizing current stimulation of the S/E cell were sufficient to produce cumulative depolarization of B cells. Precluding disinhibition of the B cell from the caudal hair cell was also found to attenuate cumulative depolarization. Additional constraints, inherent to the neural organization of the visual and statocyst neural systems were found to further limit the degree of cumulative depolarization. Among the most important of these were the interpairing interval and light intensity. Exposure of intact animals of five pairings of light and rotation resulted in short-term suppression of phototactic behavior. Like the cumulative depolarization of B cells with in vitro conditioning procedures, these changes were relatively pairing specific and persisted for comparable durations of time. Cumulative depolarization of B cells appears to be an important initial step in the production of long-term associative neural and behavioral changes in Hermissenda.

scholarly journals Local sympathetic neurons promote neutrophil egress from the bone marrow at the onset of acute inflammation

2020 ◽  
Vol 32 (11) ◽  
pp. 727-736 ◽  
Author(s):  
Tomoka Ao ◽  
Junichi Kikuta ◽  
Takao Sudo ◽  
Yutaka Uchida ◽  
Kenta Kobayashi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Immune Cells ◽  
Acute Inflammation ◽  
Sympathetic Neurons ◽  
Dependent Manner ◽  
Adrenergic Signaling ◽  
Sympathetic Nervous

Abstract The sympathetic nervous system plays critical roles in the differentiation, maturation and recruitment of immune cells under homeostatic conditions, and in responses to environmental stimuli, although its role in the migratory control of immune cells during acute inflammation remains unclear. In this study, using an advanced intravital bone imaging system established in our laboratory, we demonstrated that the sympathetic nervous system locally regulates neutrophil egress from the bone marrow for mobilization to inflammatory foci. We found that sympathetic neurons were located close to blood vessels in the bone marrow cavity; moreover, upon lipopolysaccharide (LPS) administration, local sympathectomy delayed neutrophil egress from the bone marrow and increased the proportion of neutrophils that remained in place. We also showed that vascular endothelial cells produced C-X-C motif chemokine ligand 1 (CXCL1), which is responsible for neutrophil egress out of the bone marrow. Its expression was up-regulated during acute inflammation, and was suppressed by β-adrenergic receptor blockade, which was accompanied with inhibition of neutrophil egress into the systemic circulation. Furthermore, systemic β-adrenergic signaling blockade decreased the recruitment of neutrophils in the lung under conditions of acute systemic inflammation. Taken together, the results of this study first suggested a new regulatory system, wherein local sympathetic nervous activation promoted neutrophil egress by enhancing Cxcl1 expression in bone marrow endothelial cells in a β-adrenergic signaling-dependent manner, contributing to the recruitment of neutrophils at the onset of inflammation in vivo.

scholarly journals Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

2014 ◽  
Vol 307 (9) ◽  
pp. L692-L706 ◽  
Author(s):  
Gerrit John-Schuster ◽  
Katrin Hager ◽  
Thomas M. Conlon ◽  
Martin Irmler ◽  
Johannes Beckers ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cigarette Smoke ◽  
Macrophage Activation ◽  
Cell Function ◽  
Chronic Obstructive ◽  
Dependent Manner ◽  
Tissue Destruction ◽  
Deficient Mice

Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures and macrophages accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to an increased size and number of iBALT structures, and increased lung compliance and mean linear chord length in wild-type (WT) but not in B cell-deficient mice. The increased accumulation of lung resident macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro coculture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation, which could be inhibited by an anti-IL-10 antibody. In summary, B cell function in iBALT formation seems necessary for macrophage activation and tissue destruction in CS-induced emphysema and possibly provides a new target for therapeutic intervention in COPD.

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