Investigation of Some Inflammation Related Gene Expressions Under Lipotoxic Endoplasmic Reticulum Stress In Mouse Macrophage Cell Line
Abstract
Objectives: The accumulation of free fatty acids in non-adipose tissues lead to cellular lipotoxicity and induce endoplasmic reticulum ER stress. To restore ER homeostasis, cells evoke an adaptive mechanism that is known as the unfolded protein response UPR . The aim of this study was to investigate the potential relationship between ER stress and some inflammasome complexes under lipotoxic ER stress conditions in the mouse macrophage cell line RAW 264.7 .Materials and Methods: The mouse macrophage cells RAW 264.7 were treated with Ethanol-BSA control or Palmitate-BSA 500μM . The expression of inflammation-related target genes was investigated using the qRTPCR method. Results: A significant induction at the mRNA levels of mTNFα, mNFκBIB, mIRF7, mCCL5, and reduction at the mRNA level of mIRF1 after lipid-induced metabolic ER stress were observed in RAW 264.7 cells.Conclusion: Together, these findings confirm that UPR regulates the expression of key inflammation-related genes under saturated lipid-induced stress conditions
References
- Hotamisligil GS. Endoplasmic reticulum stress and atherosclerosis. Nat Med 2010;16:396-9. [CrossRef]
- Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007;8:519-29. [CrossRef]
- Oakes SA, Papa FR. The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol 2015;10:173-94. [CrossRef]
- Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer 2014;14:581-97. [CrossRef]
- Hetz C. The unfolded protein response: Controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 2012;13:89-102. [CrossRef]
- Schröder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem 2005;74:739-89. [CrossRef]
- Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 2011;13:184-90. [CrossRef]
- Haze K, Yoshida H, Yanagi H, Yura T, Mori K. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 1999;10:3787-99. [CrossRef]
- Shen J, Chen X, Hendershot L, Prywes R. ER stress regulation of ATF6 localization by dissociation of bip/GRP78 binding and unmasking of golgi localization signals. Dev Cell 2002;3:99-111.
- Gargalovic PS, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, et al. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol 2006;26:2490-6. [CrossRef]
- Janssens S, Pulendran B, Lambrecht BN. Emerging functions of the unfolded protein response in immunity. Nat Immunol 2014;15:910- 9. [CrossRef]
- Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, Igbaria A, et al. IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab 2012;16:250-64. [CrossRef]
- Schmitz ML, Shaban MS, Albert BV, Gökçen A, Kracht M. The crosstalk of endoplasmic reticulum (ER) stress pathways with nf-κb: Complex mechanisms relevant for cancer, inflammation and infection. Biomedicines 2018; 16;6. [CrossRef]
- Lebeaupin C, Proics E, de Bieville CH, Rousseau D, Bonnafous S, Patouraux S, et al. ER stress induces NLRP3 inflammasome activation and hepatocyte death. Cell Death Dis 2015; 10;6:e1879. [CrossRef]
- Iwakoshi NN, Pypaert M, Glimcher LH. The transcription factor XBP-1 is essential for the development and survival of dendritic cells. J Exp Med 2007;204:2267-75. [CrossRef]
- Kamimura D, Bevan MJ. Endoplasmic reticulum stress regulator XBP- 1 contributes to effector CD8+ T cell differentiation during acute infection. J Immunol 2008;181:5433-41. [CrossRef]
- Pahl HL, Baeuerle PA. Activation of nf-kappa B by ER stress requires both ca2+ and reactive oxygen intermediates as messengers. FEBS Lett 1996;392:129-36. [CrossRef]
- Chen Y, Vallee S, Wu J, Vu D, Sondek J, Ghosh G. Inhibition of nf- kappab activity by ikappabbeta in association with kappab-ras. Mol Cell Biol 2004;24:3048-56. [CrossRef]
- Kim S, Joe Y, Kim HJ, Kim YS, Jeong SO, Pae HO, et al. Endoplasmic reticulum stress-induced ire1α activation mediates cross-talk of gsk-3β and XBP-1 to regulate inflammatory cytokine production. J Immunol 2015;194:4498-506. [CrossRef]
- Huang S, Rutkowsky JM, Snodgrass RG, Ono-Moore KD, Schneider DA, Newman JW, et al. Saturated fatty acids activate tlr-mediated proinflammatory signaling pathways. J Lipid Res 2012;53:2002-13. [CrossRef]
- Zhang Y, Liao S, Fan W, Wei W, Wang C, Sun S. Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells. Oncol Rep 2014;32:2769-76. [CrossRef]
- Tufanli O, Telkoparan Akillilar P, Acosta-Alvear D, Kocaturk B, Onat UI, Hamid SM, et al. Targeting IRE1 with small molecules counteracts progression of atherosclerosis. Proc Natl Acad Sci U S A 2017;114:E1395-1404. [CrossRef]
- Borradaile NM, Han X, Harp JD, Gale SE, Ory DS, Schaffer JE. Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res 2006;47:2726-37. [CrossRef]
- Nadir M, Tufanli O, Erbay E, Atalay A. Identification of differentially expressed microRNAs during lipotoxic endoplasmic reticulum stress in RAW264.7 macrophages. Turk J Biochem 2016; 41: 206–15. [CrossRef]
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 2001; 25: 402-8. [CrossRef]
- Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, et al. Fatty acid- induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 2011;12:408-15. [CrossRef]
- Zou R, Xue J, Huang Q, Dai Z, Xu Y. Involvement of receptor- interacting protein 140 in palmitate-stimulated macrophage infiltration of pancreatic beta cells. Exp Ther Med 2017;14:483-94. [CrossRef]
- Huang S, Rutkowsky JM, Snodgrass RG, Ono-Moore KD, Schneider DA, Newman JW, et al. Saturated fatty acids activate tlr-mediated proinflammatory signaling pathways. J Lipid Res 2012;53:2002-13. [CrossRef]
- Rocha DM, Bressan J, Hermsdorff HH. The role of dietary fatty acid intake in inflammatory gene expression: A critical review. Sao Paulo Med J 2017; 135:157-68. [CrossRef]
- Romeo GR, Lee J, Shoelson SE. Metabolic syndrome, insulin resistance, and roles of inflammation--mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol 2012;32:1771-6. [CrossRef]
- Kanneganti TD, Ozören N, Body-Malapel M, Amer A, Park JH, Franchi L, et al. 289 Bacterial RNA and small antiviral compounds activate caspase-1 through 290 cryopyrin/nalp3. Nature 2006;440:233-6. [CrossRef]
- Legrand-Poels S, Esser N, L’homme L, Scheen A, Paquot N, Piette J. Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes. Biochem Pharmacol 2014;92:131-41. [CrossRef]
- Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 2008;8:923-34. [CrossRef]
- Ozcan L, Tabas I. Role of endoplasmic reticulum stress in metabolic disease and other disorders. Annu Rev Med 2012;63:317-28. [CrossRef]
LİPOTOKSİK ENDOPLAZMIK STRES SONUCU İNFLAMASYON ILE İLIŞKILI BAZI GEN İFADELERININ FARE MAKROFAJ HÜCRE HATTINDA ARAŞTIRILMASI
Abstract
Amaç: Adipoz olmayan dokularda serbest yağ asitlerinin birikmesi, hücresel lipotoksisiteye ve endoplazmik retikulum ER stresine neden olur. ER homeostazını geri kazanmak için hücreler, katlanmamış protein tepkisi UPR olarak bilinen bir uyarlamalı mekanizma uyandırır. Bu çalışmada, lipotoksik ER stres koşulları altında ER stres ve bazı inflamasyon kompleksleri arasındaki moleküler ilişki fare makrofaj hücre hattında RAW 264.7 araştırılmıştır. Gereç ve Yöntem: Fare makrofaj hücreleri RAW 264.7 , Ethanol-BSA kontrol veya Palmitate-BSA 500 μM ile muamele edildi. İnflamasyonla ilişkili hedef genlerin ekspresyon değişimleri qRT-PCR yöntemi kullanılarak araştırıldı. Bulgular: RAW 264.7 hücrelerinde lipit kaynaklı metabolik ER stres sonrasında; mTNFα, mNFκBIB, mIRF7, mCCL5 mRNA seviyelerinde artış ve mIRF1 mRNA seviyesinde azalma olduğunu gözlemledi. Sonuç: Bu çalışmanın sonuçları UPR’ nin, doymuş lipit kaynaklı stres koşulları altında temel inflamasyonla ilişkili genlerin ekspresyonunu düzenlediğini doğrulamaktadır.
References
- Hotamisligil GS. Endoplasmic reticulum stress and atherosclerosis. Nat Med 2010;16:396-9. [CrossRef]
- Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007;8:519-29. [CrossRef]
- Oakes SA, Papa FR. The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol 2015;10:173-94. [CrossRef]
- Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer 2014;14:581-97. [CrossRef]
- Hetz C. The unfolded protein response: Controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 2012;13:89-102. [CrossRef]
- Schröder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem 2005;74:739-89. [CrossRef]
- Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 2011;13:184-90. [CrossRef]
- Haze K, Yoshida H, Yanagi H, Yura T, Mori K. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 1999;10:3787-99. [CrossRef]
- Shen J, Chen X, Hendershot L, Prywes R. ER stress regulation of ATF6 localization by dissociation of bip/GRP78 binding and unmasking of golgi localization signals. Dev Cell 2002;3:99-111.
- Gargalovic PS, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, et al. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol 2006;26:2490-6. [CrossRef]
- Janssens S, Pulendran B, Lambrecht BN. Emerging functions of the unfolded protein response in immunity. Nat Immunol 2014;15:910- 9. [CrossRef]
- Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, Igbaria A, et al. IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab 2012;16:250-64. [CrossRef]
- Schmitz ML, Shaban MS, Albert BV, Gökçen A, Kracht M. The crosstalk of endoplasmic reticulum (ER) stress pathways with nf-κb: Complex mechanisms relevant for cancer, inflammation and infection. Biomedicines 2018; 16;6. [CrossRef]
- Lebeaupin C, Proics E, de Bieville CH, Rousseau D, Bonnafous S, Patouraux S, et al. ER stress induces NLRP3 inflammasome activation and hepatocyte death. Cell Death Dis 2015; 10;6:e1879. [CrossRef]
- Iwakoshi NN, Pypaert M, Glimcher LH. The transcription factor XBP-1 is essential for the development and survival of dendritic cells. J Exp Med 2007;204:2267-75. [CrossRef]
- Kamimura D, Bevan MJ. Endoplasmic reticulum stress regulator XBP- 1 contributes to effector CD8+ T cell differentiation during acute infection. J Immunol 2008;181:5433-41. [CrossRef]
- Pahl HL, Baeuerle PA. Activation of nf-kappa B by ER stress requires both ca2+ and reactive oxygen intermediates as messengers. FEBS Lett 1996;392:129-36. [CrossRef]
- Chen Y, Vallee S, Wu J, Vu D, Sondek J, Ghosh G. Inhibition of nf- kappab activity by ikappabbeta in association with kappab-ras. Mol Cell Biol 2004;24:3048-56. [CrossRef]
- Kim S, Joe Y, Kim HJ, Kim YS, Jeong SO, Pae HO, et al. Endoplasmic reticulum stress-induced ire1α activation mediates cross-talk of gsk-3β and XBP-1 to regulate inflammatory cytokine production. J Immunol 2015;194:4498-506. [CrossRef]
- Huang S, Rutkowsky JM, Snodgrass RG, Ono-Moore KD, Schneider DA, Newman JW, et al. Saturated fatty acids activate tlr-mediated proinflammatory signaling pathways. J Lipid Res 2012;53:2002-13. [CrossRef]
- Zhang Y, Liao S, Fan W, Wei W, Wang C, Sun S. Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells. Oncol Rep 2014;32:2769-76. [CrossRef]
- Tufanli O, Telkoparan Akillilar P, Acosta-Alvear D, Kocaturk B, Onat UI, Hamid SM, et al. Targeting IRE1 with small molecules counteracts progression of atherosclerosis. Proc Natl Acad Sci U S A 2017;114:E1395-1404. [CrossRef]
- Borradaile NM, Han X, Harp JD, Gale SE, Ory DS, Schaffer JE. Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res 2006;47:2726-37. [CrossRef]
- Nadir M, Tufanli O, Erbay E, Atalay A. Identification of differentially expressed microRNAs during lipotoxic endoplasmic reticulum stress in RAW264.7 macrophages. Turk J Biochem 2016; 41: 206–15. [CrossRef]
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 2001; 25: 402-8. [CrossRef]
- Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, et al. Fatty acid- induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 2011;12:408-15. [CrossRef]
- Zou R, Xue J, Huang Q, Dai Z, Xu Y. Involvement of receptor- interacting protein 140 in palmitate-stimulated macrophage infiltration of pancreatic beta cells. Exp Ther Med 2017;14:483-94. [CrossRef]
- Huang S, Rutkowsky JM, Snodgrass RG, Ono-Moore KD, Schneider DA, Newman JW, et al. Saturated fatty acids activate tlr-mediated proinflammatory signaling pathways. J Lipid Res 2012;53:2002-13. [CrossRef]
- Rocha DM, Bressan J, Hermsdorff HH. The role of dietary fatty acid intake in inflammatory gene expression: A critical review. Sao Paulo Med J 2017; 135:157-68. [CrossRef]
- Romeo GR, Lee J, Shoelson SE. Metabolic syndrome, insulin resistance, and roles of inflammation--mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol 2012;32:1771-6. [CrossRef]
- Kanneganti TD, Ozören N, Body-Malapel M, Amer A, Park JH, Franchi L, et al. 289 Bacterial RNA and small antiviral compounds activate caspase-1 through 290 cryopyrin/nalp3. Nature 2006;440:233-6. [CrossRef]
- Legrand-Poels S, Esser N, L’homme L, Scheen A, Paquot N, Piette J. Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes. Biochem Pharmacol 2014;92:131-41. [CrossRef]
- Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 2008;8:923-34. [CrossRef]
- Ozcan L, Tabas I. Role of endoplasmic reticulum stress in metabolic disease and other disorders. Annu Rev Med 2012;63:317-28. [CrossRef]
There are 34 citations in total.
Details
| Primary Language | English |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | December 1, 2020 |
| Published in Issue | Year 2020Issue: 4 |