Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Role of heat shock protein 70 in regulation of anti-inflammatory response to curcumin in 3T3-L1 adipocytes

  • Sunhye Shin (Major of Food and Nutrition, Division of Applied Food System, Seoul Women's University) ;
  • Kolapo M. Ajuwon (Department of Animal Sciences, Purdue University)
  • Received : 2022.10.26
  • Accepted : 2022.12.29
  • Published : 2023.06.01
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Abstract

BACKGROUND/OBJECTIVES: Curcumin is a well-known phytochemical with anti-inflammatory effects. Heat shock protein (HSP) 70, an intracellular chaperone, inhibits proinflammatory signaling activation. Although curcumin has been shown to induce HSP70 expression in various cell types, whether HSP70 mediates the anti-inflammatory effects of curcumin in mature adipocytes remains unclear. MATERIALS/METHODS: To assess the role of HSP70 in regulating the anti-inflammatory response to curcumin in adipocytes, fully differentiated 3T3-L1 adipocytes were treated with curcumin, lipopolysaccharide (LPS), and/or the HSP70 inhibitor pifithrin-µ (PFT-µ). The expression levels of HSP70 and proinflammatory cytokines were then measured. RESULTS: Curcumin upregulated HSP70 expression at both protein and mRNA levels and attenuated LPS-induced Il6, Ptx3, and Ccl2 mRNA upregulation. PFT-µ tended to exacerbate the LPS-induced upregulation of Il6, Ptx3, Ccl2, and Tnfa mRNA expression. However, on curcumin pretreatment, the tendency of PFT-µ to upregulate LPS-induced proinflammatory cytokine expression decreased or disappeared. CONCLUSION: These results indicate that HSP70 is involved in the regulation of inflammatory responses but may not be crucial for the anti-inflammatory effects of curcumin in 3T3-L1 adipocytes.

Keywords

Acknowledgement

This work was supported by a research grant from Seoul Women's University (2021-0145).

References

  1. Pan MH, Lai CS, Dushenkov S, Ho CT. Modulation of inflammatory genes by natural dietary bioactive compounds. J Agric Food Chem 2009;57:4467-77. https://doi.org/10.1021/jf900612n
  2. Prasad S, Aggarwal B. Chronic diseases caused by chronic inflammation require chronic treatment: anti-inflammatory role of dietary spices. J Clin Cell Immunol 2014;5:238.
  3. Afman L, Milenkovic D, Roche HM. Nutritional aspects of metabolic inflammation in relation to health--insights from transcriptomic biomarkers in PBMC of fatty acids and polyphenols. Mol Nutr Food Res 2014;58:1708-20. https://doi.org/10.1002/mnfr.201300559
  4. Son TG, Camandola S, Mattson MP. Hormetic dietary phytochemicals. Neuromolecular Med 2008;10:236-46. https://doi.org/10.1007/s12017-008-8037-y
  5. Si H, Liu D. Dietary antiaging phytochemicals and mechanisms associated with prolonged survival. J Nutr Biochem 2014;25:581-91. https://doi.org/10.1016/j.jnutbio.2014.02.001
  6. Shehzad A, Ha T, Subhan F, Lee YS. New mechanisms and the anti-inflammatory role of curcumin in obesity and obesity-related metabolic diseases. Eur J Nutr 2011;50:151-61. https://doi.org/10.1007/s00394-011-0188-1
  7. Gonzales AM, Orlando RA. Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes. Nutr Metab (Lond) 2008;5:17.
  8. Jabczyk M, Nowak J, Hudzik B, Zubelewicz-Szkodzinska B. Curcumin in metabolic health and disease. Nutrients 2021;13:4440.
  9. Jalali M, Mahmoodi M, Mosallanezhad Z, Jalali R, Imanieh MH, Moosavian SP. The effects of curcumin supplementation on liver function, metabolic profile and body composition in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2020;48:102283.
  10. Chien YJ, Chang CY, Wu MY, Chen CH, Horng YS, Wu HC. Effects of curcumin on glycemic control and lipid profile in polycystic ovary syndrome: systematic review with meta-analysis and trial sequential analysis. Nutrients 2021;13:684.
  11. Wickenberg J, Ingemansson SL, Hlebowicz J. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr J 2010;9:43.
  12. Chen YC, Tsai SH, Shen SC, Lin JK, Lee WR. Alternative activation of extracellular signal-regulated protein kinases in curcumin and arsenite-induced HSP70 gene expression in human colorectal carcinoma cells. Eur J Cell Biol 2001;80:213-21. https://doi.org/10.1078/0171-9335-00158
  13. Teiten MH, Reuter S, Schmucker S, Dicato M, Diederich M. Induction of heat shock response by curcumin in human leukemia cells. Cancer Lett 2009;279:145-54. https://doi.org/10.1016/j.canlet.2009.01.031
  14. Guo M, Xu W, Yamamoto Y, Suzuki T. Curcumin increases heat shock protein 70 expression via different signaling pathways in intestinal epithelial cells. Arch Biochem Biophys 2021;707:108938.
  15. Wang J, Lee J, Liem D, Ping P. HSPA5 gene encoding Hsp70 chaperone BiP in the endoplasmic reticulum. Gene 2017;618:14-23. https://doi.org/10.1016/j.gene.2017.03.005
  16. Kim JY, Yenari MA. The immune modulating properties of the heat shock proteins after brain injury. Anat Cell Biol 2013;46:1-7.
  17. Ran R, Lu A, Zhang L, Tang Y, Zhu H, Xu H, Feng Y, Han C, Zhou G, Rigby AC, et al. Hsp70 promotes TNF-mediated apoptosis by binding IKKγ and impairing NF-κB survival signaling. Genes Dev 2004;18:1466-81. https://doi.org/10.1101/gad.1188204
  18. Ferat-Osorio E, Sanchez-Anaya A, Gutierrez-Mendoza M, Bosco-Garate I, Wong-Baeza I, Pastelin-Palacios R, Pedraza-Alva G, Bonifaz LC, Cortes-Reynosa P, Perez-Salazar E, et al. Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism. J Inflamm (Lond) 2014;11:19.
  19. Green A, Krause J, Rumberger JM. Curcumin is a direct inhibitor of glucose transport in adipocytes. Phytomedicine 2014;21:118-22. https://doi.org/10.1016/j.phymed.2013.08.014
  20. Wang N, Wang F, Gao Y, Yin P, Pan C, Liu W, Zhou Z, Wang J. Curcumin protects human adipose-derived mesenchymal stem cells against oxidative stress-induced inhibition of osteogenesis. J Pharmacol Sci 2016;132:192-200. https://doi.org/10.1016/j.jphs.2016.10.005
  21. Weisberg SP, Leibel R, Tortoriello DV. Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology 2008;149:3549-58. https://doi.org/10.1210/en.2008-0262
  22. Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W, Lu H, Fantus IG, Jin T. Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS One 2012;7:e28784.
  23. Shin SK, Ha TY, McGregor RA, Choi MS. Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism. Mol Nutr Food Res 2011;55:1829-40. https://doi.org/10.1002/mnfr.201100440
  24. Na LX, Li Y, Pan HZ, Zhou XL, Sun DJ, Meng M, Li XX, Sun CH. Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: a double-blind, placebo-controlled trial. Mol Nutr Food Res 2013;57:1569-77.
  25. Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R, Phisalaphong C, Jirawatnotai S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012;35:2121-7. https://doi.org/10.2337/dc12-0116
  26. Di Naso FC, Porto RR, Fillmann HS, Maggioni L, Padoin AV, Ramos RJ, Mottin CC, Bittencourt A, Marroni NA, de Bittencourt PI Jr. Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression. Obesity (Silver Spring) 2015;23:120-9. https://doi.org/10.1002/oby.20919
  27. Kavanagh K, Flynn DM, Jenkins KA, Zhang L, Wagner JD. Restoring HSP70 deficiencies improves glucose tolerance in diabetic monkeys. Am J Physiol Endocrinol Metab 2011;300:E894-901. https://doi.org/10.1152/ajpendo.00699.2010
  28. Gu Y, Chen J, Wang T, Zhou C, Liu Z, Ma L. Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury. Exp Ther Med 2016;12:3767-72. https://doi.org/10.3892/etm.2016.3821
  29. Tulapurkar ME, Ramarathnam A, Hasday JD, Singh IS. Bacterial lipopolysaccharide augments febrilerange hyperthermia-induced heat shock protein 70 expression and extracellular release in human THP1 cells. PLoS One 2015;10:e0118010.
  30. Zhang Y, Ma X, Jiang D, Chen J, Jia H, Wu Z, Kim IH, Yang Y. Glycine attenuates lipopolysaccharideinduced acute lung injury by regulating NLRP3 inflammasome and NRF2 signaling. Nutrients 2020;12:611.
  31. Bernardini C, Zannoni A, Turba ME, Fantinati P, Tamanini C, Bacci ML, Forni M. Heat shock protein 70, heat shock protein 32, and vascular endothelial growth factor production and their effects on lipopolysaccharide-induced apoptosis in porcine aortic endothelial cells. Cell Stress Chaperones 2005;10:340-8. https://doi.org/10.1379/CSC-98R1.1
  32. Wu S, Yano S, Chen J, Hisanaga A, Sakao K, He X, He J, Hou DX. Polyphenols from Lonicera caerulea L. berry inhibit LPS-induced inflammation through dual modulation of inflammatory and antioxidant mediators. J Agric Food Chem 2017;65:5133-41. https://doi.org/10.1021/acs.jafc.7b01599
  33. Gupta A, Cooper ZA, Tulapurkar ME, Potla R, Maity T, Hasday JD, Singh IS. Toll-like receptor agonists and febrile range hyperthermia synergize to induce heat shock protein 70 expression and extracellular release. J Biol Chem 2013;288:2756-66. https://doi.org/10.1074/jbc.M112.427336
  34. Leu JI, Pimkina J, Frank A, Murphy ME, George DL. A small molecule inhibitor of inducible heat shock protein 70. Mol Cell 2009;36:15-27. https://doi.org/10.1016/j.molcel.2009.09.023
  35. Ishaq M, Ojha R, Sharma K, Sharma G, Singh SK, Majumdar S. Functional inhibition of Hsp70 by pifithrin-µ switches Gambogic acid induced caspase dependent cell death to caspase independent cell death in human bladder cancer cells. Biochim Biophys Acta 2016;1863:2560-73. https://doi.org/10.1016/j.bbamcr.2016.07.001
  36. Sheng L, Tang T, Liu Y, Ma Y, Wang Z, Tao H, Zhang Y, Qi Z. Inducible HSP70 antagonizes cisplatin-induced cell apoptosis through inhibition of the MAPK signaling pathway in HGC-27 cells. Int J Mol Med 2018;42:2089-97. https://doi.org/10.3892/ijmm.2018.3789
  37. Salminen A, Lehtonen M, Paimela T, Kaarniranta K. Celastrol: molecular targets of thunder god vine. Biochem Biophys Res Commun 2010;394:439-42. https://doi.org/10.1016/j.bbrc.2010.03.050
  38. Paimela T, Hyttinen JM, Viiri J, Ryhanen T, Karjalainen RO, Salminen A, Kaarniranta K. Celastrol regulates innate immunity response via NF-κB and Hsp70 in human retinal pigment epithelial cells. Pharmacol Res 2011;64:501-8. https://doi.org/10.1016/j.phrs.2011.05.027
  39. Ohnishi K, Nakahata E, Irie K, Murakami A. Zerumbone, an electrophilic sesquiterpene, induces cellular proteo-stress leading to activation of ubiquitin-proteasome system and autophagy. Biochem Biophys Res Commun 2013;430:616-22. https://doi.org/10.1016/j.bbrc.2012.11.104
  40. Igarashi Y, Ohnishi K, Irie K, Murakami A. Possible contribution of zerumbone-induced proteo-stress to its anti-inflammatory functions via the activation of heat shock factor 1. PLoS One 2016;11:e0161282.