Immunomodulatory Effect of Curcumin in the Upregulation of Inflammasome Pathway Genes Induced by Sulfur Mustard Analog: An In-vitro Study Curcumin Effect in Upregulated Inflammasome Genes

Sulfur Mustard (SM) induces cell injury via exerting oxidative stress, protease-anti protease imbalance, and inflammation. Inflammasome as one part of innate immunity has a critical role in the recognition of cell injuries and the initiation of the inflammation process by releasing IL-1β. Hence, the...

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Published in:Iranian journal of allergy, asthma, and immunology asthma, and immunology, 2021-01, Vol.20 (2), p.169
Main Authors: Chehardoli, Baharak, Nadi, Mona, Ali Khamis Abadi, Azam Kia, Shahriary, Alireza, Salimian, Jafar
Format: Article
Language:English
Subjects:
Anti-inflammatory agents
Caspase-1
Cell injury
Curcumin
Epithelial cells
Gene expression
IL-1β
Immunomodulation
Inflammasomes
Inflammation
Innate immunity
Lethal dose
Lymphocytes B
Mustard gas
Oxidative stress
Proteinase
Pyrin protein
Sulfur
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container_title Iranian journal of allergy, asthma, and immunology
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creator Chehardoli, Baharak
Nadi, Mona
Ali Khamis Abadi
Azam Kia
Shahriary, Alireza
Salimian, Jafar
description Sulfur Mustard (SM) induces cell injury via exerting oxidative stress, protease-anti protease imbalance, and inflammation. Inflammasome as one part of innate immunity has a critical role in the recognition of cell injuries and the initiation of the inflammation process by releasing IL-1β. Hence, the present study investigated the effects of the sub-lethal doses of 2-chloroethyl ethyl sulfide (CEES) as SM analog on the gene expression level of inflammasome-related genes as well as the potential protective effects of curcumin on this process. The effects of sub-lethal doses (500, 1000, and 2500 mM) of CEES on pulmonary epithelial cell line (A549) were determined at various time points (12, 24, and 48 h). Following the treatment of cells with CEES, the kinetic alterations of the expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells(NF-ĸB1), NLR family pyrin domain containing 1 (NLRP1), Caspase-1 (Casp1),andInterleukin-1β (IL-1β) genes were analyzed; using real-time PCR. In addition, the concurrent protective effects of different doses of curcumin (20, 40, 80, and 160 mM) on modulating the effects of CEES were studied. Although it was found that the lowest sub-lethal dose of CEES (500 mM) was able to up-regulate the inflammasome-related genes, the maximum alterations occurred 48 h after the treatment with the higher sub-lethal dose (2500 mM) of CEES. The maximum alteration occurred in Casp1 (38 fold), IL-1β (19 fold), and NLRP1(~4 fold) genes (p
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Inflammasome as one part of innate immunity has a critical role in the recognition of cell injuries and the initiation of the inflammation process by releasing IL-1β. Hence, the present study investigated the effects of the sub-lethal doses of 2-chloroethyl ethyl sulfide (CEES) as SM analog on the gene expression level of inflammasome-related genes as well as the potential protective effects of curcumin on this process. The effects of sub-lethal doses (500, 1000, and 2500 mM) of CEES on pulmonary epithelial cell line (A549) were determined at various time points (12, 24, and 48 h). Following the treatment of cells with CEES, the kinetic alterations of the expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells(NF-ĸB1), NLR family pyrin domain containing 1 (NLRP1), Caspase-1 (Casp1),andInterleukin-1β (IL-1β) genes were analyzed; using real-time PCR. In addition, the concurrent protective effects of different doses of curcumin (20, 40, 80, and 160 mM) on modulating the effects of CEES were studied. Although it was found that the lowest sub-lethal dose of CEES (500 mM) was able to up-regulate the inflammasome-related genes, the maximum alterations occurred 48 h after the treatment with the higher sub-lethal dose (2500 mM) of CEES. The maximum alteration occurred in Casp1 (38 fold), IL-1β (19 fold), and NLRP1(~4 fold) genes (p&lt;0.0001). However, the NF-ĸB gene expression level did not alter following CEES exposure. Even though low doses of curcumin (20, 40, and 80 mM) were able to down-regulate the studied genes, it was found that the treatment of cells with 160 mM of curcumin for 48 h was able to normalize the expression level of all genes. 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Inflammasome as one part of innate immunity has a critical role in the recognition of cell injuries and the initiation of the inflammation process by releasing IL-1β. Hence, the present study investigated the effects of the sub-lethal doses of 2-chloroethyl ethyl sulfide (CEES) as SM analog on the gene expression level of inflammasome-related genes as well as the potential protective effects of curcumin on this process. The effects of sub-lethal doses (500, 1000, and 2500 mM) of CEES on pulmonary epithelial cell line (A549) were determined at various time points (12, 24, and 48 h). Following the treatment of cells with CEES, the kinetic alterations of the expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells(NF-ĸB1), NLR family pyrin domain containing 1 (NLRP1), Caspase-1 (Casp1),andInterleukin-1β (IL-1β) genes were analyzed; using real-time PCR. In addition, the concurrent protective effects of different doses of curcumin (20, 40, 80, and 160 mM) on modulating the effects of CEES were studied. Although it was found that the lowest sub-lethal dose of CEES (500 mM) was able to up-regulate the inflammasome-related genes, the maximum alterations occurred 48 h after the treatment with the higher sub-lethal dose (2500 mM) of CEES. The maximum alteration occurred in Casp1 (38 fold), IL-1β (19 fold), and NLRP1(~4 fold) genes (p&lt;0.0001). However, the NF-ĸB gene expression level did not alter following CEES exposure. Even though low doses of curcumin (20, 40, and 80 mM) were able to down-regulate the studied genes, it was found that the treatment of cells with 160 mM of curcumin for 48 h was able to normalize the expression level of all genes. The present study concludes that curcumin as an anti-inflammatory agent may have beneficial immunomodulatory effects following CEES exposure.</abstract><cop>Tehran</cop><pub>Tehran University of Medical Sciences</pub><doi>10.18502/ijaai.v20i2.6050</doi></addata></record>
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subjects Anti-inflammatory agents
Caspase-1
Cell injury
Curcumin
Epithelial cells
Gene expression
IL-1β
Immunomodulation
Inflammasomes
Inflammation
Innate immunity
Lethal dose
Lymphocytes B
Mustard gas
Oxidative stress
Proteinase
Pyrin protein
Sulfur
title Immunomodulatory Effect of Curcumin in the Upregulation of Inflammasome Pathway Genes Induced by Sulfur Mustard Analog: An In-vitro Study Curcumin Effect in Upregulated Inflammasome Genes
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