scholarly journals Liriodendrin alleviates sciatic endometriosis-associated pain in rats via suppressing inflammatory response and regulating the signaling pathway of Pl3K/Akt/mToR

Author(s):  
Jianfang Gong ◽  
Liangliang Xue ◽  
Mengling Wei ◽  
Wenli Han ◽  
Shen Jing

IntroductionLY294002 has been validated as a PI3K pan-inhibitor in the pathogenesis of airway inflammation, which attenuated IL-25-induced asthma-like AHR. Liriodendrin was proved to play essential roles in attenuating endometriosis-associated pain. This work aimed to gain a mechanical insight into the therapeutic efficiency of Liriodendrin administration on attenuating endometriosis-associated pain.Material and methodsVon Frey filament test and thermal hyperalgesia test were carried out to evaluate the acute and daily efficiency of drug administration. Western blot was used to analyze the expression of substance P, PI3K/AKT/mTOR, p-PI3K/p-AKT/p-mTOR, and CGRP. ELISA was performed to examine interleukin-1, interleukin-2, interleukin-6, TNF-α and PGE2 levels.ResultsAs a result, Liriodendrin significantly attenuated pain in endometriosis rats and restored the up-regulation of p-PI3K/p-AKT/p-mTOR in the endometriosis rats. The increased interleukin-1, interleukin-2, interleukin-6, TNF-α, and PGE2 levels were remarkably restored by Liriodendrin in endometriosis rats. Moreover, the activated expression of substance P in the ventral horn of the spinal cord of endometriosis rats was notably restored by Liriodendrin in addition to CGRP. Furthermore, Liriodendrin effectively restored the LPS induced up-regulation of p-PI3K/p-AKT/p-mTOR protein as well as the LPS activated IL-6, TNF-α, and IL-1β mRNA and protein expression in 12Z cells.ConclusionsWe found that compared with LY294200, Liriodendrin exerted a more evident therapeutic effect in the treatment of endometriosis-associated pain by suppressing the secretion of pro-inflammatory cytokines.

2017 ◽  
Vol 37 (02) ◽  
pp. 120-123 ◽  
Author(s):  
K. Krüger
Keyword(s):  

ZusammenfassungBiologika werden in der Rheumatologie seit 17 Jahren eingesetzt. Sie haben die Behandlungsmöglichkeiten bei Krankheiten wie der rheumatoiden Arthritis (RA) dramatisch verbessert und entscheidend dazu beigetragen, dass heute die Remission bei dieser Erkrankung das Behandlungsziel darstellt. Gegenwärtig sind aus dieser Wirkstoffgruppe neun Substanzen für die Behandlung der RA zugelassen, fünf davon hemmen TNF-α, je eines Interleukin-1, Interleukin-6, B-Lymphozyten und die Aktivierung von T-Lymphozyten. Zusätzlich stehen aktuell drei Infliximab-Bio -similars und ein Etanercept-Biosimilar zur Verfügung. Biologika kommen bei der RA bei Patienten mit ungünstiger Prognose als Zweitlinientherapie (in der Regel im Fall einer nicht ausreichend wirksamen Starttherapie mit Methotrexat = MTX) zum Einsatz, in den übrigen Fällen sollten sie bei Versagen konventioneller DMARDs spätestens als Drittlinientherapie eingesetzt werden. Sie sollten kombiniert mit MTX verwendet werden, so-fern dieser Kombinationspartner zur Verfügung steht. Bei MTX-Kontraindikation oder -Unverträglichkeit sind einige der Substanzen auch für die Monotherapie zugelassen, die beste Wirksamkeit bieten hier Tocilizumab und in zweiter Linie Etanercept. Bei Unwirksamkeit des ersten Biologikums ist ein Switch auf eine andere Substanz aus der Gruppe oft erfolgreich.


Perfusion ◽  
2005 ◽  
Vol 20 (5) ◽  
pp. 263-268 ◽  
Author(s):  
Gianluca Brancaccio ◽  
Emmanuel Villa ◽  
Elia Girolami ◽  
Guido Michielon ◽  
Cristiana Feltri ◽  
...  

Cardiac surgery with cardiopulmonary bypass (CPB) elicits an inflammatory response and has a multitude of biological consequences, ranging from subclinical organ dysfunction to severe multiorgan failure. Pediatric patients are more prone to have a reaction that can jeopardize their outcome. Cytokines are supposed to be important mediators in this response: limiting their circulating levels is, therefore, appealing. We investigated the pattern of cytokine release during pediatric operation for congenital heart anomalies in 20 patients, and the effect of hemofiltration. Tumor necrosis factor a (TNF-α) was elevated after anesthesia induction and showed significant decrease during CPB. Hemofiltration reduced its concentration, but the effect disappeared on the following day. Interleukin-1 (IL-1) increased slowly at the end of CPB and hemofiltration had no effect. Interleukin-6 (IL-6) showed a tendency toward augmentation during rewarming and hemofiltration did not significantly affect the course. Soluble interleukin-6 receptor (sIL-6r) had a pattern similar to TNF-α, but hemofiltration had no effect. On the other hand, interleukin-8 (IL-8) behaved like IL-6. Our findings suggest that baseline clinical status, anesthetic drugs, and maneuvers before incision may elicit a cytokine response, whereas rewarming is a critical phase of CPB. Hemofiltration is effective in removal of TNF-α, but its role is debatable for the control of IL-1, IL-6, sIL-6r and IL-8 levels.


2013 ◽  
Vol 59 (1) ◽  
pp. 31-35
Author(s):  
Zsuzsánna Réti ◽  
Iz Kun ◽  
Corina Cristina Radu Pop

Abstract Background: Graves’ orbitopathy (GO) is considered an autoimmune condition in close relationship with Graves’ disease (GD) affecting the thyroid. Several similarities exist between the two conditions, sharing the common antigen and the characteristics of the inflammation mediated by a number of cytokines. The result of the immune reactions will lead to the expansion of adipose tissue, production of glycosaminoglycans and soft tissue inflammation. Material and methods: In our study we examined the serum level of interleukin-1 (IL-1), interleukin 2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) in correlation with the activity of disease and smoking habits in 25 patients with GD and GO. Results: We found that smokers had higher serum IL-6 and lower serum MCP-1, IL-8 and TNF-α level compared to non-smokers. Also, we found a weak positive correlation between serum IL-10, IFN-γ and disease activity (clinical activity score, CAS) and negative correlation between serum IL-1 and activity. Conclusion: Our findings support the fact that some cytokines (IL-10, IFN-γ, IL-1) play a role in active disease, while others are influenced by environmental factors, such as smoking (IL-6, IL-8, TNF-α). The discrepancy of cytokine profiles may reflect different patient characteristics, such as disease stage and disease activity and determination of serum cytokines would be useful in selecting patients who need more aggressive treatment protocols.


2012 ◽  
Vol 24 (1) ◽  
pp. 187
Author(s):  
B. C. Yang ◽  
K. C. Hwang ◽  
K. W. Kim ◽  
H. C. Lee ◽  
H. J. Chung ◽  
...  

The putative mouse homologue of cytochrome P-450 4F16 (Cyp4f16) is induced by interleukin-1 (Il-1), interleukin-6 (Il-6) and tumour necrosis factor-α (Tnf-α) and repressed by interleukin-10 (Il-10) and lipopolysaccharide (LPS). The Cyp4F16 is a subfamily of Cyp4F and it is also related to eicosanoids that are important mediators in the inflammatory cascade (Cui et al. 2001). To investigate the role of Cyp4F16, in the present study, we report the production of Cyp4f16 gene knock-down mice in 2 strains of mice, namely A/J and C57BL/6. The A/J is susceptible to infection and it is associated with Cyp4F16, whereas C57BL/6 is relatively resistant to infection. An shRNA-Cyp4F16 expression vector was microinjected into pronuclei of fertilized mouse oocytes and the embryos were transferred into pseudopregnant recipients. As a result, 25 and 50 mice were produced in the A/J and C57BL, respectively. Two mice in the A/J strain and 6 in the C57BL strain were confirmed by PCR as transgenic. Organs were collected in each of the lines produced by inbreeding and screened with real-time PCR for Cyp4f16 transcripts. The Cyp4f16 gene was expressed in a tissue-specific manner with high expression in the pancreas, spleen and lung and a lower level of transcription in the heart, muscle, thymus, kidney, testis and liver. In the spleen of transgenic Cyp4f16 knock-down mice, Cyp4f16 mRNA and protein expression levels were significantly lower than those of wild-type mice. The A/J Cyp4f16 knock-down mice suffered an inflammatory skin disease and tumours, but wild-type A/J mice and knock-down C57BL mice did not. Taken together, these results suggest that Cyp4f16 may play a regulatory role in the immune system and point to the use of the Cyp4f16 knock-down mouse as an experimental animal model for the study of the inflammatory process. This work was supported by a grant PJ0070762010 from BioGreen 21 Program, Rural Development Administration, Republic of Korea.


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