Effect Of Cholinergic Anti-inflammatory Pathway Research Articles

The effects of the cholinergic system on carrageenan-induced arthritis

The cholinergic system has been found to make an anti-inflammatory effect through the cholinergic anti-inflammatory pathway (CAIP), which suppresses the production of pro-inflammatory cytokines by secreting acetylcholine, a major neurotransmitter. However, no studies have been conducted on the effects of CAIP on joint pain and inflammation. In this study, we investigated the effects of muscarinic acetylcholine receptors (mAChRs) in knee arthritis. To examine pain behavioral changes, atropine (or saline for sham control) was pretreated in the joint cavity of rats at 1 % carrageenan + 5, 10, and 30 μL and the dynamic weight-bearing evaluation was performed. Synovial membranes were collected and cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β) were measured using a western blot. Hematoxylin and eosin staining was performed. Compared to that of the sham group, the weight-bearing of the affected knee joint significantly increased in the 1 % carrageenan + 10 μL atropine group (p < 0.05). However, no significant changes were observed in the 1 % carrageenan + 5 and 30 μL atropine groups. COX-2 and IL-1β and the number of inflammatory cells in synovial membrane significantly increased with 1 % carrageenan + 10 μL of atropine (p < 0.05). These results suggest that cholinergic system is involved in knee joint pain and inflammation and that mAChRs are potential therapeutic targets for knee joint arthritis.

Role of Cholinergic Anti-Inflammatory Pathway in Protecting Sepsis-Induced Acute Lung Injury through Regulation of the Conventional Dendritic Cells.

Background The cholinergic anti-inflammatory pathway connects the immune response system and the nervous system via the vagus nerve. The key regulatory receptor is the α7-subtype of the nicotinic acetylcholine receptor (α7nAChR). Cholinergic anti-inflammatory pathway has been proved to be effective in suppressing the inflammation responses in acute lung injury (ALI). Dendritic cells (DCs), the important antigen-presenting cells, also express the α7nAChR. Past studies have indicated that reducing the quantity of mature conventional DCs and inhibiting the maturation of pulmonary DCs may prove effective for the treatment of ALI. However, the effects of cholinergic anti-inflammatory pathway on maturation, function, and quantity of DCs and conventional DCs in ALI remain unclear. Objective It was hypothesized that cholinergic anti-inflammatory pathway may inhibit the inflammatory response of ALI by regulating maturation, phenotype, and quantity of DCs and conventional DCs. Methods GTS-21 (GTS-21 dihydrochloride), an α7nAchR agonist, was prophylactically administered in sepsis-induced ALI mouse model and LPS-primed bone marrow-derived dendritic cells. The effects of GTS-21 were observed with respect to maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2 (type 2 conventional DCs) and the release of DC-related proinflammatory cytokines in vivo and in vitro. Results The results of the present study revealed that GTS-21 treatment decreased the maturation of DCs and the production of DC-related proinflammatory cytokines in vitro and in sepsis-induced ALI mouse model; it reduced the quantity of CD11c+MHCII+ conventional DCs and CD11c+CD11b+ conventional DCs2 in vivo experiment. Conclusions Cholinergic anti-inflammatory pathway contributes to the reduction in the inflammatory response in ALI by regulating maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2.

Choline and citicoline ameliorate oxidative stress in acute kidney injury in rats.

The purpose of this study is to investigate the effects of cholinergic anti-inflammatory pathway (CAP)-activating drugs, choline and citicoline (Cytidinediphosphate-choline, CDP-choline), on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) parameters and the contribution of NADPH Oxidase4 (NOX4) p22phox. Endotoxemia induces a systemic inflammatory response characterized by the production of pro-inflammatory mediators and reactive oxygen species (ROS), which eventually develops acute kidney injury (AKI). NADPH Oxidase4 (NOX4) p22phox pathway contributes to the development of endotoxemia-induced AKI. Inflammatory response can be controlled by CAP. Expressions levels of KIM-1, TNF-α, NOX4, p22phox and NFκB in the kidney tissues of rats were analyzed via RT-PCR in experimental groups; 1. Control, 2. LPS (10 mg/kg) + saline, 3. LPS + CDP-choline (375 mg/kg) and 4. LPS + choline (90 mg/kg). Choline and ROS levels in kidney tissues were also measured by a spectrofluorometric assay. LPS-induced elevations of ROS levels were decreased by CDP-choline or choline administration (p < 0.001). LPS-elevated KIM-1, TNFα, NOX4, p22 phox, and NFκB expressions were significantly decreased by choline or CDP-choline treatments (p < 0.001). Decreased ROS production in kidney tissues in treatment groups suggests that choline or CDP-choline may have therapeutic potential in endotoxemia-associated AKI via downregulating NOX4 and p22phox expressions (Tab. 1, Fig. 5, Ref. 45). Text in PDF www.elis.sk Keywords: endotoxemia, choline, cytidine diphosphate choline, acute kidney injury, reactive oxygen species.

Advances in the research of effects of cholinergic anti-inflammatory pathway on vital organ function and its mechanism

Serious major burns, trauma and surgical stress can easily develop into sepsis, and further result in septic shock or even multiple organ dysfunction syndrome (MODS). The mechanism of MODS is complicated, including excessive inflammation, immune dysfunction, coagulation disorder, and ischemia-reperfusion injury. Recent studies have demonstrated that the nervous system could significantly and quickly suppress systemic inflammatory response via the vagus nerve, which might improve multiple organ damage following acute injury. This article is to brief our understanding concerning the structure characteristics of cholinergic anti-inflammatory pathway, and its effects on vital organ function and the regulatory mechanism, which might be of great significance to seek a novel way for interventional strategy of MODS.

Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine

The cholinergic anti-inflammatory pathway can inhibit the inflammation of collagen induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). However, the immunologic mechanisms that provide a therapeutic effect against the auto-inflammatory disease are not yet elucidated. The present study explores the effect of cholinergic anti-inflammatory pathway on CD4+ T cell responses in CIA. Forty DBA/1 mice were divided into 4 groups: a control group, a CIA group, a vagotomy group, and a nicotine group. The degree of arthritis was measured by arthritis score and hematoxylin and eosin. ELISA was used to detect the serum concentration of IFN-γ, IL-4 and IL-17A. Flow cytometry was used to detect the cytokines and transcription factors (TFs) (the TFs of Th1, Th2, and Th17 cells are T-bet, RORγτ and GATA3 respectively) in the spleen. Immunohistochemistry was used to analyze RORγτ expression in the joint synovium. Arthritis in the nicotine group was significantly lightened compared with that in the CIA group and in the vagotomy group. Nicotine attenuated Th17 lineage by reducing IL-17A production and RORγτ expression. The expressions of IL-4 and GATA3 were increased in the same setting. However, the expressions of IFN-γ and T-bet had no difference between the nicotine and the CIA group. Nicotine may induce a shift to the Th2 lineage and improve the Th1/Th2 imbalance. Activating the cholinergic anti-inflammatory pathway with nicotine can inhibit Th17 cell responses and may improve the Th1/Th2 imbalance in CIA, providing a new justification for its application in the treatment of rheumatoid arthritis.

Effects of cholinergic anti-inflammatory pathway on ventilator-induced lung injury in rats

To investigate the effects of cholinergic anti-inflammatory pathway on ventilator-induced lung injury (VILI) in rats. Thirty-six healthy Sprague-Dawley (SD) rats were randomly divided into three groups: control group, in which rats did not receive ventilation; high-tidal volume (HVT) ventilation group; nicotine treatment (HVT+nicotine) group, in which rats received intraperitoneal injection of nicotine (2 mg/kg) 10 minutes before HVT ventilation; equal amount of normal saline was given to rats in other two groups. A rat model of VILI was reproduced by volume-controlled mechanical ventilation with HVT. Hemodynamic parameters were measured throughout the study period. Arterial blood gases were measured every 1 hour. After maintaining ventilation for 2 hours, rats were sacrificed and lung tissue specimens were harvested. Lung wet-dry weight ratio (W/D) and myeloperoxidase (MPO) activity were measured. Interleukin-8 (IL-8) level in bronchoalveolar lavage fluid (BALF) and intercellular adhesion molecule-1 (ICAM-1) level in lung tissue homogenate were measured by enzyme-linked immunosorbent assay (ELISA), respectively. After hematoxylin and eosin (HE) staining, pathological examination of lung tissue was performed, and diffuse alveolar damage (DAD) score was estimated. Mean pH of arterial blood in HVT group and HVT+nicotine group tended to be higher than the baseline value during the ventilation. Mean partial pressure of oxygen in arterial blood (PaO2), mean partial pressure of carbon dioxide in arterial blood (PaCO2), and mean arterial pressure (MAP) in HVT group and HVT+nicotine group were lower than baseline value during the ventilation. Mean PaO2 (mm Hg, 1 mm Hg=0.133 kPa) in HVT+nicotine group was significantly higher than that in HVT group after 2 hours of ventilation (85+/-4 vs. 76+/-3, P<0.05). Mean W/D ratio and mean MPO activity in HVT group were significantly higher than those in control group [W/D ratio: 5.66+/-0.33 vs. 4.53+/-0.21, P<0.01; MPO (U/g): 1.73+/-0.50 vs. 0.89+/-0.17, P<0.05]. Mean W/D ratio (5.02+/-0.37) and mean MPO activity (1.11+/-0.33) in HVT+nicotine group were significantly lower than those in HVT group (both P<0.05). Compared with control group, DAD scores in HVT group and HVT+nicotine group (10.40+/-1.85, 7.90+/-1.67 vs. 1.60+/-1.20), IL-8 concentration (ng/L: 1 625.3+/-271.7, 965.5+/-310.5 vs. 428.5+/-120.6) and ICAM-1 concentration (microg/L: 589.4+/-87.5, 452.5+/-89.3 vs. 247.5+/-73.7) were significantly higher (all P<0.01). But DAD score, IL-8 concentration, ICAM-1 concentration in HVT+nicotine group were significantly lower than those in HVT group (P<0.05 or P<0.01). Activation of cholinergic anti-inflammatory pathway can protect the lung against VILI by suppressing IL-8 and ICAM-1 expression, inhibiting neutrophil aggregation and infiltration.

W1723 Protective Effect of Cholinergic Anti-Inflammatory Pathway Against Acute Esophagitis in Rats

W1723 Protective Effect of Cholinergic Anti-Inflammatory Pathway Against Acute Esophagitis in Rats

Protective effects of cholinergic anti-inflammatory pathway against acute esophagitis in rats

Protective effects of cholinergic anti-inflammatory pathway against acute esophagitis in rats