Profiling on Altered Productions of Cytokines or Chemokines from THP-1 Cell Line Following in Vitro Exposure to Cyclophosphamide, Cyclosporine, Dexamethasone, or Tacrolimus, Representative Immunosuppressants
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Although immune suppressive drugs have contributed for the cancer chemotherapy, organ transplant, but their therapeutic efficacy is limited. This study aims to evaluate the immunological modulations induced by four representative immunosuppressive on THP-1 cell line. 75% cell viabilities were determined and four test concentrations, 0.01X, 0.1X, 0.5X, and vehicle control were chosen. Culture supernatants were collected at 24 h after lipopolysaccharide (LPS1 ㎍/㎖) activation in the presence of test substances. 27 target cytokines were measured through luminex system and relative cytokine production levels (RCPLs,%) were calculated. Cytokines with the RCPL below 100% at all the three concentrations were 21 including IL-1beta, -1ra, -2, -4, -5, -6, -7, -9, -10, -12, -13, -15, -17, Eotaxin, FGF-basic, GM-CSF, IFNγ, IP-10, MCP-1α, PDGF-BB, and VEGF in dexamethasone-treated cells. Concerning on cyclophosphamide, the RCPLs on 11 cytokines were less than 100% at all the 3 concentrations. Treatment of cyclosporine demonstrated 10 cytokines with below 100% RCPL at all the 3 concentrations. The RCPLs below 100% were observed with 22 cytokines including IL-1β, -1ra, -2, -4, -5, -6, -7, -9, -12, -13, -15, -17, Eotaxin, GFG-basic, G-CSF, GM-CSF, IFNγ, MCP-1, MIP-1α, PDGF-BB, TNFα, a nd VEGF from THP-1 cells t reated w ith tacrolimus a t all the 3 concentrations. The present study indicates that tacrolimus and dexamethasone are stronger immunosuppressants than cyclophosphamide and cyclosporine on THP-1 cell line.
Abstract
Although immune suppressive drugs have contributed for the cancer chemotherapy, organ transplant, but their therapeutic efficacy is limited. This study aims to evaluate the immunological modulations induced by four representative immunosuppressive on THP-1 cell line. 75% cell viabilities were determined and four test concentrations, 0.01X, 0.1X, 0.5X, and vehicle control were chosen. Culture supernatants were collected at 24 h after lipopolysaccharide (LPS1 ㎍/㎖) activation in the presence of test substances. 27 target cytokines were measured through luminex system and relative cytokine production levels (RCPLs,%) were calculated. Cytokines with the RCPL below 100% at all the three concentrations were 21 including IL-1beta, -1ra, -2, -4, -5, -6, -7, -9, -10, -12, -13, -15, -17, Eotaxin, FGF-basic, GM-CSF, IFNγ, IP-10, MCP-1α, PDGF-BB, and VEGF in dexamethasone-treated cells. Concerning on cyclophosphamide, the RCPLs on 11 cytokines were less than 100% at all the 3 concentrations. Treatment of cyclosporine demonstrated 10 cytokines with below 100% RCPL at all the 3 concentrations. The RCPLs below 100% were observed with 22 cytokines including IL-1β, -1ra, -2, -4, -5, -6, -7, -9, -12, -13, -15, -17, Eotaxin, GFG-basic, G-CSF, GM-CSF, IFNγ, MCP-1, MIP-1α, PDGF-BB, TNFα, a nd VEGF from THP-1 cells t reated w ith tacrolimus a t all the 3 concentrations. The present study indicates that tacrolimus and dexamethasone are stronger immunosuppressants than cyclophosphamide and cyclosporine on THP-1 cell line.
참고문헌 (25)
- Akdis M, "Interleukins(from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α : receptors, functions, and roles in diseases", J. Allergy Clin. Immunol, 138, pp.984~1010 (2016)
- Ahlmann M, "The effect of cyclophosphamide on the immune system : implications for clinical cancer therapy", Cancer Chemother. Pharmacol, 78, pp.661~671 (2016)
- Bianchi M, "Inhibition of IL-2-induced Jak-STAT signaling by glucocorticoids", PNAS, 97, pp.9573~9578 (2000)
- Brazelton TR, "Molecular mechanisms of action of new xenobiotic immunosuppressive drugs : tacrolimus(FK506), sirolimus(rapamycin), mycophenolate mofetil and leflunomide", Curr. Opin. Immunol, 8, pp.710~720 (1996)
- Cavallasca JA, "Severe infections in patients with autoimmune disease treated with cyclophosphamide", Reumatol. Clin, 11, pp.221~223 (2015)
- Cilião HL, "Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells", Exp. Toxicol. Pathol, 67, pp.179~187 (2015)
- Coecke S, "Guidance on good cell culture practice. A report of the second ECVAM task force on good cell culture practice", ATLA, 33, pp.1~27 (2005)
- Diehl R, "Immunosuppression for in vivo research : state-of-the-art protocols and experimental approaches", Cell. Mol. Immunol, 14, pp.146~179 (2017)
- Gennari A, "The Use of In Vitro Systems for Evaluating Immunotoxicity: The Report and Recommendations of an ECVAM Workshop", J. Immunotoxicol, 2, pp.61~83 (2005)
- Giles AJ, "Dexamethasone-induced immunosuppression : mechanisms and implications for immunotherapy", J. ImmunoTher. Cancer, 6, pp.51~ (2018)
- Gong JH, "Dexamethasone enhances the antitumor efficacy of Gemcitabine by glucocorticoid receptor signaling", Cancer Biol. Ther, 21, pp.332~343 (2020)
- Hartung T, "Immunotoxicology : Challenges in the 21st century and in vitro opportunities", ALTEX, 30, pp.411~426 (2013)
- Hinton DM., "Immunotoxicity testing applied to direct food and colour additives : US FDA’Redbook II’ guidelines", Hum. Exp. Toxicol, 14, pp.143~145 (1995)
- Hirano T., "Cellular pharmacodynamics of immunosuppressive drugs for individualized medicine", Int. Immunopharmacol, 7, pp.3~22 (2007)
- Lankveld DP, "In Vitro testing for Direct Immunotoxicity : State of the Art", Methods Mol. Biol, 598, pp.401~423 (2010)
- Matsuda S, "Mechanisms of action of cyclosporine", Immunopharmacology, 47, pp.119~125 (2000)
- Naesens M, "Calcineurin inhibitor nephrotoxicity", Clin. J. Am. Soc. Nephrol, 4, pp.481~508 (2009)
- Pointon JC, "Thalidomide enhances cyclophosphamide and dexamethasone mediated cytotoxicity towards cultured chronic lymphocytic leukaemia cells", Oncol. Rep, 24, pp.1315~1321 (2010)
- Shoughy SS, "Efficacy and safety of low-dose topical tacrolimus in vernal keratoconjunctivitis", Clin. Ophthalmol, 10, pp.643~647 (2016)
- Tongu M, "Immunogenic chemotherapy with cyclophosphamide and doxorubicin against established murine carcinoma", Cancer Immunol. Immunother, 59, pp.769~777 (2010)
- Wang H, "Dexamethasone as a chemoprotectant in cancer chemotherapy : hematoprotective effects and altered pharmacokinetics and tissue distribution of carboplatin and gemcitabine", Cancer Chemother. Pharmacol, 53, pp.459~467 (2004)
- Wang H, "Dexamethasone as a chemosensitizer for breast cancer chemotherapy : potentiation of the antitumor activity of adriamycin, modulation of cytokine expression, and pharmacokinetics", Int. J. Oncol, 30, pp.947~953 (2007)
- Winkelstein A, "Mechanism of Immunosuppression : Effects of Cyclophosphamide on Cellular Immunity", Blood, 41, pp.273~284 (1973)
- Zhai J, "Tacrolimus in the treatment of ocular diseases", BioDrugs, 25, pp.89~103 (2011)
- Zhang W, "Recent topics on the mechanisms of immunosuppressive therapy-related neurotoxicities", Int. J. Mol. Sci, 20, pp.3210~ (2019)