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

Baharak Chehardoli; Mona Nadi; Ali  Khamis Abadi; Azam Kia; Alireza Shahriary; Jafar Salimian

doi:10.18502/ijaai.v20i2.6050

Baharak Chehardoli Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
Mona Nadi Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
Ali Khamis Abadi Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Azam Kia Basic Science School, East Tehran Branch, Payame Noor University, Tehran, Iran
Alireza Shahriary Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Jafar Salimian Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v20i2.6050

Keywords: Curcumin; Genes; Inflammasomes; Sulfur mustard; 2-chloroethyl ethyl sulfide

Abstract

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-chainenhancer of activated B cells (NF-ĸB1), NLR family pyrin domain containing 1 (NLRP1), Caspase-1 (Casp1), and Interleukin-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 upregulate 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<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.