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Therapeutic efficacy of carboxyamidotriazole on 2,4,6-trinitrobenzene sulfonic acid-induced colitis model is associated with the inhibition of NLRP3 inflammasome and NF-κB activation.
Int Immunopharmacol. 2017 Apr; 45:16-25.II

Abstract

Excess proinflammatory cytokines owing to the activation of NF-κB and NLRP3 inflammasome play the key role in inflammatory bowel disease (IBD). Previously, we reported the anti-inflammatory activity of carboxyamidotriazole (CAI) resulting from decreasing cytokines. Therefore, we investigated the therapeutic effects of CAI in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat colitis and the involvement of CAI action with NLRP3 inflammasome and NF-κB pathway. CAI was orally administered to TNBS-induced colitis rat. The severity of colitis was assessed, and NLRP3 inflammasome, NF-κB pathway and cytokines were determined. Our results showed that CAI significantly reduced weight loss and disease activity index (DAI) scores in colitis rats and alleviated the colonic macroscopic signs and pathological damage. In addition, the intestinal inflammatory markers and permeability index were markedly ameliorated by CAI treatment. The decreased levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-18 were also detected in the colon tissues of CAI-treated colitis rats. Moreover, the activation of NLRP3 inflammasome in inflamed colon was significantly suppressed by showing an obvious reduction in the NLRP3 and activated caspase-1 levels. Furthermore, CAI reduced NF-κB p65 expression and IκBα phosphorylation and degradation in colitis rats. Therefore, CAI attenuates TNBS-induced colitis, which may be attributed to its inhibition of NLRP3 inflammasome and NF-κB activation, and down-regulation of proinflammatory cytokines. These results provide further understanding of the intestinal anti-inflammatory effect of CAI and highlight it as a potential drug for the treatment of IBD.

Authors+Show Affiliations

Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China. Electronic address: leizhu2004@126.com.Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China. Electronic address: caiyingye@126.com.

Pub Type(s)

Evaluation Study
Journal Article

Language

eng

PubMed ID

28152446

Citation

Du, Xiaowan, et al. "Therapeutic Efficacy of Carboxyamidotriazole On 2,4,6-trinitrobenzene Sulfonic Acid-induced Colitis Model Is Associated With the Inhibition of NLRP3 Inflammasome and NF-κB Activation." International Immunopharmacology, vol. 45, 2017, pp. 16-25.
Du X, Chen W, Wang Y, et al. Therapeutic efficacy of carboxyamidotriazole on 2,4,6-trinitrobenzene sulfonic acid-induced colitis model is associated with the inhibition of NLRP3 inflammasome and NF-κB activation. Int Immunopharmacol. 2017;45:16-25.
Du, X., Chen, W., Wang, Y., Chen, C., Guo, L., Ju, R., Li, J., Zhang, D., Zhu, L., & Ye, C. (2017). Therapeutic efficacy of carboxyamidotriazole on 2,4,6-trinitrobenzene sulfonic acid-induced colitis model is associated with the inhibition of NLRP3 inflammasome and NF-κB activation. International Immunopharmacology, 45, 16-25. https://doi.org/10.1016/j.intimp.2017.01.015
Du X, et al. Therapeutic Efficacy of Carboxyamidotriazole On 2,4,6-trinitrobenzene Sulfonic Acid-induced Colitis Model Is Associated With the Inhibition of NLRP3 Inflammasome and NF-κB Activation. Int Immunopharmacol. 2017;45:16-25. PubMed PMID: 28152446.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic efficacy of carboxyamidotriazole on 2,4,6-trinitrobenzene sulfonic acid-induced colitis model is associated with the inhibition of NLRP3 inflammasome and NF-κB activation. AU - Du,Xiaowan, AU - Chen,Wei, AU - Wang,Yufeng, AU - Chen,Chen, AU - Guo,Lei, AU - Ju,Rui, AU - Li,Juan, AU - Zhang,Dechang, AU - Zhu,Lei, AU - Ye,Caiying, Y1 - 2017/01/31/ PY - 2016/11/03/received PY - 2016/12/07/revised PY - 2017/01/10/accepted PY - 2017/2/6/pubmed PY - 2017/6/2/medline PY - 2017/2/3/entrez KW - Carboxyamidotriazole KW - Inflammatory bowel disease KW - NF-κB KW - NLRP3 inflammasome KW - TNBS rat colitis SP - 16 EP - 25 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 45 N2 - Excess proinflammatory cytokines owing to the activation of NF-κB and NLRP3 inflammasome play the key role in inflammatory bowel disease (IBD). Previously, we reported the anti-inflammatory activity of carboxyamidotriazole (CAI) resulting from decreasing cytokines. Therefore, we investigated the therapeutic effects of CAI in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat colitis and the involvement of CAI action with NLRP3 inflammasome and NF-κB pathway. CAI was orally administered to TNBS-induced colitis rat. The severity of colitis was assessed, and NLRP3 inflammasome, NF-κB pathway and cytokines were determined. Our results showed that CAI significantly reduced weight loss and disease activity index (DAI) scores in colitis rats and alleviated the colonic macroscopic signs and pathological damage. In addition, the intestinal inflammatory markers and permeability index were markedly ameliorated by CAI treatment. The decreased levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-18 were also detected in the colon tissues of CAI-treated colitis rats. Moreover, the activation of NLRP3 inflammasome in inflamed colon was significantly suppressed by showing an obvious reduction in the NLRP3 and activated caspase-1 levels. Furthermore, CAI reduced NF-κB p65 expression and IκBα phosphorylation and degradation in colitis rats. Therefore, CAI attenuates TNBS-induced colitis, which may be attributed to its inhibition of NLRP3 inflammasome and NF-κB activation, and down-regulation of proinflammatory cytokines. These results provide further understanding of the intestinal anti-inflammatory effect of CAI and highlight it as a potential drug for the treatment of IBD. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/28152446/Therapeutic_efficacy_of_carboxyamidotriazole_on_246_trinitrobenzene_sulfonic_acid_induced_colitis_model_is_associated_with_the_inhibition_of_NLRP3_inflammasome_and_NF_κB_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(17)30023-1 DB - PRIME DP - Unbound Medicine ER -