Research Article
İturin A'nın Parkinson hastalığının 6-OHDA kaynaklı SH-SY5Y hücre modelinde anti-inflamatuar etkileri
Abstract
Amaç: Bakteriler tarafından üretilen biyosürfaktanlar, terapötik ve biyomedikal potansiyel sunan antibakteriyel, antifungal ve antiviral özellikleri nedeniyle özellikle önemlidir. Bununla birlikte, hiçbir araştırma Bacillus türevi biyosürfaktan İturin A'nın Parkinson hastalığı üzerindeki etkisini incelememiştir. Bu çalışma, Parkinson hastalığı için yeni bir terapötik yaklaşım formüle etmek amacıyla İturin A'nın sitokin aracılı nöroprotektif etkisini incelemiştir.
Gereç ve Yöntem: İturin A'nın SH-SY5Y hücrelerindeki hücre canlılığı üzerindeki etkisi MTT [3-(4,5-Dimetil tiyazol-2) 2,5-difeniltetrazolium bromür] yöntemi ile değerlendirilmiştir. MTT deneyinin sonucunda, toksik olmayan doz hücre canlılığı (%) ile belirlendi. İturin A'nın nöroprotektif etkisini değerlendirmek için, SH-SY5Y hücreleri toksik olmayan bir doz Iturin A ile muamele edildi ve ardından 6-OHDA ile indüklendi. Bu muamelelerden sonra, SH-SY5Y hücrelerindeki sitokinler (IL-6, TGF-β) ve kemokin (IL-8) ELISA kiti ile değerlendirildi. Tüm verileri analiz etmek için GraphPad Prism 9 kullanıldı.
Bulgular: İturin A ile 48 saatlik tedavi, sitokinlerin (IL-6, TGF-β) ve kemokin (IL-8) ifade seviyelerini değiştirerek 6-OHDA ile indüklenen SH-SY5Y hücrelerinde nöroprotektif bir etki gösterdi (p<0,05 - p<0,0001).
Sonuç: Iturin A, Parkinson hastalarının tedavisinde yeni yaklaşımlar sunabilir ve in vitro sonuçları doğrulamak için ek in vivo çalışmalara ihtiyaç vardır.
Keywords
References
- Mirzaei H, Sedighi S, Kouchaki E, Barati E, Dadgostar E, Aschner M, et al. Probiotics and the Treatment of Parkinson’s Disease: An Update. Cell Mol Neurobiol 2023;42(8):2449.
- Guo S, Wang H, Yin Y. Microglia Polarization From M1 to M2 in Neurodegenerative Diseases. Front Aging Neurosci 2022;14:815347.
- Guo M, Wang J, Zhao Y, Feng Y, Han S, Dong Q, et al. Microglial exosomes facilitate α-synuclein transmission in Parkinson’s disease. Brain 2020;143(5):1476
- Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm Suppl 2000;(60):277–90.
- Fahn S, Sulzer D. Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx 2004;1(1):139–54.
- Litteljohn D, Hayley S. Cytokines as Potential Biomarkers for Parkinson’s Disease: A Multiplex Approach. Methods in Molecular Biology 2012;934:121–44.
- Chen Y, Mateski J, Gerace L, Wheeler J, Burl J, Prakash B, et al. Non-coding RNAs and neuroinflammation: implications for neurological disorders. Exp Biol Med 2024;249:10120.
- Di La,zzaro G, Picca A, Boldrini S, Bove F, Marzetti E, Petracca M, et al. Differential profiles of serum cytokines in Parkinson’s disease according to disease duration. Neurobiol Dis. 2024; 1;190:106371.
- Rocha NP, De Miranda AS, Teixeira AL. Insights into Neuroinflammation in Parkinson’s Disease: From Biomarkers to Anti-Inflammatory Based Therapies. Biomed Res Int 2015;2015(1):628192.
- Li Y, Yang Y, Zhao A, Luo N, Niu M, Kang W, et al. Parkinson’s disease peripheral immune biomarker profile: a multicentre, cross-sectional and longitudinal study. J Neuroinflammation 2022 ;19(1).
- Lopert P, Patel M. Mitochondrial mechanisms of redox cycling agents implicated in Parkinson’s disease. J Neural Transm. 2016;123(2):113–23.
- Nwabufo CK, Aigbogun OP. Diagnostic and therapeutic agents that target alpha-synuclein in Parkinson’s disease. Journal of Neurology 2022;269(11):5762–86.
- Houghton PJ, Howes MJ. Natural products and derivatives affecting neurotransmission relevant to Alzheimer’s and Parkinson’s disease. Neurosignals 2005;14(1–2):6–22.
- Ohadi M, Forootanfar H, Dehghannoudeh N, Banat IM, Dehghannoudeh G. The role of surfactants and biosurfactants in the wound healing process: a review. 2023;32 (Sup4a):xxxix–xivı.
- Rodrigues L, Banat IM, Teixeira J, Oliveira R. Biosurfactants: potential applications in medicine. J Antimicrob Chemother 2006;57(4):609–18.
- Sharma P, Sharma N. Microbial Biosurfactants-an Ecofriendly Boon to Industries for Green Revolution. Recent Pat Biotechnol. 2019;14(3):169–83.
- Banat IM, De Rienzo MAD, Quinn GA. Microbial biofilms: biosurfactants as antibiofilm agents. Appl Microbiol Biotechnol 2014;98(24):9915–29.
- Zhao H, Shao D, Jiang C, Shi J, Li Q, Huang Q, et al. Biological activity of lipopeptides from Bacillus. Appl Microbiol Biotechnol. 2017;101(15):5951–60.
- Meena KR, Kanwar SS. Lipopeptides as the antifungal and antibacterial agents: applications in food safety and therapeutics. Biomed Res Int 2015;2015;473050.
- Zhao H, Yan L, Guo L, Sun H, Huang Q, Shao D, et al. Effects of Bacillus subtilis iturin A on HepG2 cells in vitro and vivo. AMB Express 2021;11(1).
- Yaraguppi DA;, Bagewadi ZK;, Patil NR;, Kowalczyk T, Sitarek P, Yaraguppi DA, et al. Iturin: A Promising Cyclic Lipopeptide with Diverse Applications. Bio mol. 2023; 13(10):1515.
- Altin-Celik P, Eken A, Derya-Andeden M, Eciroglu H, Uzen R, Donmez-Altuntas H. Iturin A and Gramicidin A inhibit proliferation, trigger apoptosis, and regulate inflammation in breast cancer cells. J Drug Deliv Sci Technol. 2024;100:106121.
- Dey G, Bharti R, Ojha PK, Pal I, Rajesh Y, Banerjee I, et al. Therapeutic implication of “Iturin A” for targeting MD-2/TLR4 complex to overcome angiogenesis and invasion. Cell Sig. 2017;35:24–36.
- Xicoy H, Wieringa B, Martens GJM. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Mol Neurodegener 2017;12(1):1–11.
- Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 2007;68(5):384–86.
- Zhou ZD, Jankovic J, Ashizawa T, Tan EK. Neurodegenerative diseases associated with non-coding CGG tandem repeat expansions. Nat Rev Neurol 2022;18(3):145–57
- Hill DR, Huters AD, Towne TB, Reddy RE, Fogle JL, Voight EA, et al. Parkinson’s Disease: Advances in Treatment and the Syntheses of Various Classes of Pharmaceutical Drug Substances. Chem Rev 2023;123(23):13693–712.
- Murakami H, Shiraishi T, Umehara T, Omoto S, Iguchi Y. Recent Advances in Drug Therapy for Parkinson’s Disease. Intern Med 2023;62(1):33–42.
- Hoye AT, Davoren JE, Wipf P, Fink MP, Kagan VE. Targeting mitochondria. Acc Chem Res 2008;41(1):87–97.
- Bradley LH, Fuqua J, Richardson A, Cholewo JT, Ai Y, Kelps KA, et al. Dopamine Neuron Stimulating Actions of a GDNF Propeptide. PLoS One 2010;5(3):e9752.
- Subramaniam SR, Chesselet MF. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol 2013;0:17.
- Hernandez-Baltazar D, Zavala-Flores LM, Villanueva-Olivo A. The 6-hydroxydopamine model and parkinsonian pathophysiology: Novel findings in an older model. Neurología (English Edition) 2017;32(8):533–39.
- Ioghen OC, Ceafalan LC, Popescu BO. SH-SY5Y Cell Line In Vitro Models for Parkinson Disease Research-Old Practice for New Trends. J Integr Neurosci 2023;22(1).
- Sznejder-Pachołek A, Joniec-Maciejak I, Wawer A, Ciesielska A, Mirowska-Guzel D. The effect of α-synuclein on gliosis and IL-1α, TNFα, IFNγ, TGFβ expression in murine brain. Pharmacological Reports. 2017;69(2):242–51.
- Weng L, Zhang H, Li X, Zhan H, Chen F, Han L, et al. Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-κB and JAK2/STAT3 signaling pathways in microglia. Int Immunopharmacol. 2017 Mar 1;44:1–8.
- Lee DS, Kwon KH, Cheong SH. Taurine Chloramine Suppresses LPS-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglial Cells. Adv Exp Med Biol 2017;975(1):131–43.
- Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson’s disease. Journal of Neural Transmission, Supplement. 2000;(60):277–90.
- Erta M, Quintana A, Hidalgo J. Interleukin-6, a Major Cytokine in the Central Nervous System. Int J Biol Sci 2012;8(9):1254.
- Vawter MP, Dillon-Carter O, Tourtellotte WW, Carvey P, Freed WJ. TGFbeta1 and TGFbeta2 concentrations are elevated in Parkinson’s disease in ventricular cerebrospinal fluid. Exp Neurol 1996;142(2):313–22.
- Rehfeldt SCH, Silva J, Alves C, Pinteus S, Pedrosa R, Laufer S, et al. Neuroprotective Effect of Luteolin-7-O-Glucoside against 6-OHDA-Induced Damage in Undifferentiated and RA-Differentiated SH-SY5Y Cells. Int J Mol Sci 2022;23(6):2914.
- Shkundin A, Halaris A. IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions. J Pers Med 2024;14(5).
- Atta-ur-Rahman, K H, RA S. Interleukin-8: An autocrine inflammatory mediator. Curr Pharm Des 1999;5(4):241–53.
- Qazi BS, Tang K, Qazi A. Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis. Int J Inflam 2011;2011:1–13.
- Liu Z, Chen HQ, Huang Y, Qiu YH, Peng YP. Transforming growth factor-β1 acts via TβR-I on microglia to protect against MPP(+)-induced dopaminergic neuronal loss. Brain Behav Immun 2016;51:131–43.
- Tesseur I, Nguyen A, Chang B, Li L, Woodling NS, Wyss-Coray T, et al. Deficiency in Neuronal TGF-β Signaling Leads to Nigrostriatal Degeneration and Activation of TGF-β Signaling Protects against MPTP Neurotoxicity in Mice. JNeurosci 2017;37(17):4584.
Anti-inflammatory effects of Iturin A on the 6-OHDA-induced SH-SY5Y cell model of Parkinson’s disease
Abstract
Aim: Biosurfactants produced by bacteria are particularly important due to their antibacterial, antifungal, and antiviral properties, which offer therapeutic and biomedical potential. Nevertheless, no research has examined the impact of Bacillus-derived biosurfactant Iturin A on Parkinson's disease. This study examined the neuroprotection through cytokine modulation of Iturin A to formulate a novel therapeutic approach for Parkinson's disease.
Materials and Methods: The effect of Iturin A on cell viability in SH-SY5Y cells was evaluated by the [3-(4,5-Dimethyl thiazole-2) 2,5-diphenyltetrazolium bromide] method. As a result of this experiment, the non-toxic dose was determined by cell viability (%). To evaluate the neuroprotective effect of Iturin A, SH-SY5Y cells were treated with a non-toxic dose of Iturin A and then induced with 6-OHDA. After these treatments, cytokines (interleukin 6, transforming growth factor beta) and chemokine (interleukin 8) in SH-SY5Y cells were evaluated by ELISA kit. GraphPad Prism 9 was used to analyze all data.
Results: Using one-way ANOVA and Dunn's post hoc test, normally distributed data was tested for multiple comparisons. Treatment with Iturin A for 48 hours showed a neuroprotective effect on 6-hydroxy dopamine-induced SH-SY5Y cells by statistically significantly decreasing the expression levels of interleukin 6 (P<0.001), transforming growth factor beta (P<0.001), and interleukin 8 (P<0.0001).
Conclusion: Iturin A might offer new approaches to treating Parkinson's patients, and additional in vivo studies are necessary to confirm the in vitro results.
Keywords
References
- Mirzaei H, Sedighi S, Kouchaki E, Barati E, Dadgostar E, Aschner M, et al. Probiotics and the Treatment of Parkinson’s Disease: An Update. Cell Mol Neurobiol 2023;42(8):2449.
- Guo S, Wang H, Yin Y. Microglia Polarization From M1 to M2 in Neurodegenerative Diseases. Front Aging Neurosci 2022;14:815347.
- Guo M, Wang J, Zhao Y, Feng Y, Han S, Dong Q, et al. Microglial exosomes facilitate α-synuclein transmission in Parkinson’s disease. Brain 2020;143(5):1476
- Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm Suppl 2000;(60):277–90.
- Fahn S, Sulzer D. Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx 2004;1(1):139–54.
- Litteljohn D, Hayley S. Cytokines as Potential Biomarkers for Parkinson’s Disease: A Multiplex Approach. Methods in Molecular Biology 2012;934:121–44.
- Chen Y, Mateski J, Gerace L, Wheeler J, Burl J, Prakash B, et al. Non-coding RNAs and neuroinflammation: implications for neurological disorders. Exp Biol Med 2024;249:10120.
- Di La,zzaro G, Picca A, Boldrini S, Bove F, Marzetti E, Petracca M, et al. Differential profiles of serum cytokines in Parkinson’s disease according to disease duration. Neurobiol Dis. 2024; 1;190:106371.
- Rocha NP, De Miranda AS, Teixeira AL. Insights into Neuroinflammation in Parkinson’s Disease: From Biomarkers to Anti-Inflammatory Based Therapies. Biomed Res Int 2015;2015(1):628192.
- Li Y, Yang Y, Zhao A, Luo N, Niu M, Kang W, et al. Parkinson’s disease peripheral immune biomarker profile: a multicentre, cross-sectional and longitudinal study. J Neuroinflammation 2022 ;19(1).
- Lopert P, Patel M. Mitochondrial mechanisms of redox cycling agents implicated in Parkinson’s disease. J Neural Transm. 2016;123(2):113–23.
- Nwabufo CK, Aigbogun OP. Diagnostic and therapeutic agents that target alpha-synuclein in Parkinson’s disease. Journal of Neurology 2022;269(11):5762–86.
- Houghton PJ, Howes MJ. Natural products and derivatives affecting neurotransmission relevant to Alzheimer’s and Parkinson’s disease. Neurosignals 2005;14(1–2):6–22.
- Ohadi M, Forootanfar H, Dehghannoudeh N, Banat IM, Dehghannoudeh G. The role of surfactants and biosurfactants in the wound healing process: a review. 2023;32 (Sup4a):xxxix–xivı.
- Rodrigues L, Banat IM, Teixeira J, Oliveira R. Biosurfactants: potential applications in medicine. J Antimicrob Chemother 2006;57(4):609–18.
- Sharma P, Sharma N. Microbial Biosurfactants-an Ecofriendly Boon to Industries for Green Revolution. Recent Pat Biotechnol. 2019;14(3):169–83.
- Banat IM, De Rienzo MAD, Quinn GA. Microbial biofilms: biosurfactants as antibiofilm agents. Appl Microbiol Biotechnol 2014;98(24):9915–29.
- Zhao H, Shao D, Jiang C, Shi J, Li Q, Huang Q, et al. Biological activity of lipopeptides from Bacillus. Appl Microbiol Biotechnol. 2017;101(15):5951–60.
- Meena KR, Kanwar SS. Lipopeptides as the antifungal and antibacterial agents: applications in food safety and therapeutics. Biomed Res Int 2015;2015;473050.
- Zhao H, Yan L, Guo L, Sun H, Huang Q, Shao D, et al. Effects of Bacillus subtilis iturin A on HepG2 cells in vitro and vivo. AMB Express 2021;11(1).
- Yaraguppi DA;, Bagewadi ZK;, Patil NR;, Kowalczyk T, Sitarek P, Yaraguppi DA, et al. Iturin: A Promising Cyclic Lipopeptide with Diverse Applications. Bio mol. 2023; 13(10):1515.
- Altin-Celik P, Eken A, Derya-Andeden M, Eciroglu H, Uzen R, Donmez-Altuntas H. Iturin A and Gramicidin A inhibit proliferation, trigger apoptosis, and regulate inflammation in breast cancer cells. J Drug Deliv Sci Technol. 2024;100:106121.
- Dey G, Bharti R, Ojha PK, Pal I, Rajesh Y, Banerjee I, et al. Therapeutic implication of “Iturin A” for targeting MD-2/TLR4 complex to overcome angiogenesis and invasion. Cell Sig. 2017;35:24–36.
- Xicoy H, Wieringa B, Martens GJM. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Mol Neurodegener 2017;12(1):1–11.
- Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 2007;68(5):384–86.
- Zhou ZD, Jankovic J, Ashizawa T, Tan EK. Neurodegenerative diseases associated with non-coding CGG tandem repeat expansions. Nat Rev Neurol 2022;18(3):145–57
- Hill DR, Huters AD, Towne TB, Reddy RE, Fogle JL, Voight EA, et al. Parkinson’s Disease: Advances in Treatment and the Syntheses of Various Classes of Pharmaceutical Drug Substances. Chem Rev 2023;123(23):13693–712.
- Murakami H, Shiraishi T, Umehara T, Omoto S, Iguchi Y. Recent Advances in Drug Therapy for Parkinson’s Disease. Intern Med 2023;62(1):33–42.
- Hoye AT, Davoren JE, Wipf P, Fink MP, Kagan VE. Targeting mitochondria. Acc Chem Res 2008;41(1):87–97.
- Bradley LH, Fuqua J, Richardson A, Cholewo JT, Ai Y, Kelps KA, et al. Dopamine Neuron Stimulating Actions of a GDNF Propeptide. PLoS One 2010;5(3):e9752.
- Subramaniam SR, Chesselet MF. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol 2013;0:17.
- Hernandez-Baltazar D, Zavala-Flores LM, Villanueva-Olivo A. The 6-hydroxydopamine model and parkinsonian pathophysiology: Novel findings in an older model. Neurología (English Edition) 2017;32(8):533–39.
- Ioghen OC, Ceafalan LC, Popescu BO. SH-SY5Y Cell Line In Vitro Models for Parkinson Disease Research-Old Practice for New Trends. J Integr Neurosci 2023;22(1).
- Sznejder-Pachołek A, Joniec-Maciejak I, Wawer A, Ciesielska A, Mirowska-Guzel D. The effect of α-synuclein on gliosis and IL-1α, TNFα, IFNγ, TGFβ expression in murine brain. Pharmacological Reports. 2017;69(2):242–51.
- Weng L, Zhang H, Li X, Zhan H, Chen F, Han L, et al. Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-κB and JAK2/STAT3 signaling pathways in microglia. Int Immunopharmacol. 2017 Mar 1;44:1–8.
- Lee DS, Kwon KH, Cheong SH. Taurine Chloramine Suppresses LPS-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglial Cells. Adv Exp Med Biol 2017;975(1):131–43.
- Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson’s disease. Journal of Neural Transmission, Supplement. 2000;(60):277–90.
- Erta M, Quintana A, Hidalgo J. Interleukin-6, a Major Cytokine in the Central Nervous System. Int J Biol Sci 2012;8(9):1254.
- Vawter MP, Dillon-Carter O, Tourtellotte WW, Carvey P, Freed WJ. TGFbeta1 and TGFbeta2 concentrations are elevated in Parkinson’s disease in ventricular cerebrospinal fluid. Exp Neurol 1996;142(2):313–22.
- Rehfeldt SCH, Silva J, Alves C, Pinteus S, Pedrosa R, Laufer S, et al. Neuroprotective Effect of Luteolin-7-O-Glucoside against 6-OHDA-Induced Damage in Undifferentiated and RA-Differentiated SH-SY5Y Cells. Int J Mol Sci 2022;23(6):2914.
- Shkundin A, Halaris A. IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions. J Pers Med 2024;14(5).
- Atta-ur-Rahman, K H, RA S. Interleukin-8: An autocrine inflammatory mediator. Curr Pharm Des 1999;5(4):241–53.
- Qazi BS, Tang K, Qazi A. Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis. Int J Inflam 2011;2011:1–13.
- Liu Z, Chen HQ, Huang Y, Qiu YH, Peng YP. Transforming growth factor-β1 acts via TβR-I on microglia to protect against MPP(+)-induced dopaminergic neuronal loss. Brain Behav Immun 2016;51:131–43.
- Tesseur I, Nguyen A, Chang B, Li L, Woodling NS, Wyss-Coray T, et al. Deficiency in Neuronal TGF-β Signaling Leads to Nigrostriatal Degeneration and Activation of TGF-β Signaling Protects against MPTP Neurotoxicity in Mice. JNeurosci 2017;37(17):4584.
There are 45 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Basic Immunology |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | June 10, 2025 |
| Submission Date | November 8, 2024 |
| Acceptance Date | January 10, 2025 |
| Published in Issue | Year 2025Volume: 64 Issue: 2 |
