LARP7 upregulates SIRT1 deacetylase activity and inhibits Th1/Th17 cytokine response in psoriatic mice
Main Article Content
Keywords
deacetylase, LARP7, psoriasis, SIRT1, Th1/Th17
Abstract
Objective: To investigate the possible role of La ribonucleoprotein 7 (LARP7) in psoriasis through a mouse model and uncover its underlying mechanism.
Methods: The back skin of C57BL/6 mice was smeared with IMquimod (IMQ) cream for 7 days to induce psoriasis. Immunoblot kit was used to detect the deacetylase activity of SIRT1 (member of sirtuin family). Hematoxylin and eosin staining was used to assess the degree of psoriasis in mouse. Flow cytometry assays were performed to confirm effects on Th1/Th17 cell differentiation. Enzyme-linked-immunosorbent serologic assays were used to detect the level of secreted cytokines.
Results: LARP7 upregulated SIRT1 deacetylase activity. LARP7 alleviated psoriasis symptoms in mice by upregulating SIRT1 deacetylase activity. In addition, LARP7 regulated Th1/Th17 cell differentiation in psoriatic mice. We further found that LARP7 inhibited Th1/Th17 cytokine.
Conclusion: LARP7 upregulated SIRT1 activity and inhibited Th1/Th17 cytokine response in psoriatic mice.
References
1. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370(9583):263–71. 10.1016/S0140-6736(07)61128-3
2. Krupka-Olek M, Bozek A, Drewienkowska M, Dryjka K, Medrala A. Immunological differences between atopic dermatitis, psoriasis, and their combination in adult patients. Allergol Immunopathol (Madr). 2022;50(4):143–6. 10.15586/aei.v50i4.557
3. Chen C, Yi X, Liu P, Li J, Yan B, Zhang D, et al. CD147 facilitates the pathogenesis of psoriasis through glycolysis and H3K9me3 Modification in keratinocytes. Research (Wash DC). 2023;6:167. 10.34133/research.0167
4. Li J, Yan W, Ren F, Sang H. Tectorigenin inhibits inflammation in keratinocytes by inhibition of NLRP3 inflammasome regulated by the TLR4/NF-kappaB pathway. Allergol Immunopathol (Madr). 2023;51(2):82–9. 10.15586/aei.v51i2.780
5. Liu L, Huan L, Zhang Y, Wei W, Chen Z, Xu D, et al. Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-kappaB pathways. Allergol Immunopathol (Madr). 2022;50(2):96–103. 10.15586/aei.v50i2.568
6. Sigurgrimsdottir H, Bjornsdottir EO, Eysteinsdottir JH, Olafsson JH, Sigurgeirsson B, Agnarsson BA, et al. Keratinocytes secrete multiple inflammatory and immune biomarkers which are regulated by LL-37 in a psoriasis mimicking microenvironment. Scand J Immunol. 2021;94(6):e13096. 10.1111/sji.13096
7. Doo C, Bao L, Shen K, Yang JF, Shen RR, Chan LS. Diacerein alone and in combination with infliximab suppresses the combined proinflammatory effects of IL-17A, IL-22, oncostatin M, IL-1A, and TNF-alpha in keratinocytes: A potential therapeutic option in psoriasis. J Interferon Cytokine Res. 2021;41(8):302–6. 10.1089/jir.2021.0036
8. Markert A, Grimm M, Martinez J, Wiesner J, Meyerhans A, Meyuhas O, et al. The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes. EMBO Rep. 2008;9(6):569–75. 10.1038/embor.2008.72
9. Ji X, Lu H, Zhou Q, Luo K. LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis. Elife. 2014;3:e02907. 10.7554/eLife.02907
10. Muniz L, Egloff S, Kiss T. RNA elements directing in vivo assembly of the 7SK/MePCE/Larp7 transcriptional regulatory snRNP. Nucleic Acids Res. 2013;41(8):4686–98. 10.1093/nar/gkt159
11. Yuan Z, Hu H, Zhu Y, Zhang W, Fang Q, Qiao T, et al. Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-κB pathway to promote metastasis. Cell Death Dis. 2021;12(6):543. 10.1038/s41419-021-03823-4
12. Li N, Liu Y. LARP7 alleviates psoriasis symptoms in mice by regulating the SIRT1/NF-kappaB signaling pathway. Allergol Immunopathol (Madr). 2023;51(1):140–5. 10.15586/aei.v51i1.765
13. Guo J, Xue H, Zhong H, Sun W, Zhao S, Meng J, et al. Involvement of LARP7 in activation of SIRT1 to inhibit NF-kappaB signaling protects microglia from acrylamide-induced neuroinflammation. Neurotox Res. 2022;40(6):2016–26. 10.1007/s12640-022-00624-1
14. Yan P, Li Z, Xiong J, Geng Z, Wei W, Zhang Y, et al. LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity. Cell Rep. 2021;37(8):110038. 10.1016/j.celrep.2021.110038
15. Wang P, Mo Z, Zhang Y, Guo C, Chikede TK, Chen D, et al. Serum IL-5 levels predict HBsAg seroclearance in patients treated with nucleos(t)ide analogues combined with pegylated interferon. Front Immunol. 2022;13:1104329. 10.3389/fimmu.2022.1104329
16. Xu F, Xu J, Xiong X, Deng Y. Salidroside inhibits MAPK, NF-kappaB, and STAT3 pathways in psoriasis-associated oxidative stress via SIRT1 activation. Redox Rep. 2019;24(1):70–4. 10.1080/13510002.2019.1658377
17. Wang MJ, Huang HJ, Xu YY, Vos H, Gulersonmez C, Stigter E, et al. Metabolic rewiring in keratinocytes by miR-31-5p identifies therapeutic intervention for psoriasis. EMBO Mol Med. 2023;15(4):e15674. 10.15252/emmm.202215674
18. Luan Y, Liu H, Luan Y, Yang Y, Yang J, Ren KD. New insight in HDACs: Potential therapeutic targets for the treatment of atherosclerosis. Front Pharmacol. 2022;13:863677. 10.3389/fphar.2022.863677
19. Zhang G, Xia Z, Tian C, Xia A, You J, Liu J, et al. Discovery of 5-((1H-indazol-3-yl) methylene)-2-thioxoimidazolidin-4-one derivatives as a new class of AHR agonists with anti-psoriasis activity in a mouse model. Bioorg Med Chem Lett. 2023;92:129383. 10.1016/j.bmcl.2023.129383
20. Sui X, Sui Y, Wang Y. LARP7 in papillary thyroid carcinoma induces NIS expression through suppression of the SHH signaling pathway. Mol Med Rep. 2018;17(6):7521–8. 10.3892/mmr.2018.8856
21. Uchikawa E, Natchiar KS, Han X, Proux F, Roblin P, Zhang E, et al. Structural insight into the mechanism of stabilization of the 7SK small nuclear RNA by LARP7. Nucleic Acids Res. 2015;43(6):3373–88. 10.1093/nar/gkv173
22. Stein S, Lohmann C, Schafer N, Hofmann J, Rohrer L, Besler C, et al. SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis. Eur Heart J. 2010;31(18):2301–9. 10.1093/eurheartj/ehq107
2. Krupka-Olek M, Bozek A, Drewienkowska M, Dryjka K, Medrala A. Immunological differences between atopic dermatitis, psoriasis, and their combination in adult patients. Allergol Immunopathol (Madr). 2022;50(4):143–6. 10.15586/aei.v50i4.557
3. Chen C, Yi X, Liu P, Li J, Yan B, Zhang D, et al. CD147 facilitates the pathogenesis of psoriasis through glycolysis and H3K9me3 Modification in keratinocytes. Research (Wash DC). 2023;6:167. 10.34133/research.0167
4. Li J, Yan W, Ren F, Sang H. Tectorigenin inhibits inflammation in keratinocytes by inhibition of NLRP3 inflammasome regulated by the TLR4/NF-kappaB pathway. Allergol Immunopathol (Madr). 2023;51(2):82–9. 10.15586/aei.v51i2.780
5. Liu L, Huan L, Zhang Y, Wei W, Chen Z, Xu D, et al. Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-kappaB pathways. Allergol Immunopathol (Madr). 2022;50(2):96–103. 10.15586/aei.v50i2.568
6. Sigurgrimsdottir H, Bjornsdottir EO, Eysteinsdottir JH, Olafsson JH, Sigurgeirsson B, Agnarsson BA, et al. Keratinocytes secrete multiple inflammatory and immune biomarkers which are regulated by LL-37 in a psoriasis mimicking microenvironment. Scand J Immunol. 2021;94(6):e13096. 10.1111/sji.13096
7. Doo C, Bao L, Shen K, Yang JF, Shen RR, Chan LS. Diacerein alone and in combination with infliximab suppresses the combined proinflammatory effects of IL-17A, IL-22, oncostatin M, IL-1A, and TNF-alpha in keratinocytes: A potential therapeutic option in psoriasis. J Interferon Cytokine Res. 2021;41(8):302–6. 10.1089/jir.2021.0036
8. Markert A, Grimm M, Martinez J, Wiesner J, Meyerhans A, Meyuhas O, et al. The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes. EMBO Rep. 2008;9(6):569–75. 10.1038/embor.2008.72
9. Ji X, Lu H, Zhou Q, Luo K. LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis. Elife. 2014;3:e02907. 10.7554/eLife.02907
10. Muniz L, Egloff S, Kiss T. RNA elements directing in vivo assembly of the 7SK/MePCE/Larp7 transcriptional regulatory snRNP. Nucleic Acids Res. 2013;41(8):4686–98. 10.1093/nar/gkt159
11. Yuan Z, Hu H, Zhu Y, Zhang W, Fang Q, Qiao T, et al. Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-κB pathway to promote metastasis. Cell Death Dis. 2021;12(6):543. 10.1038/s41419-021-03823-4
12. Li N, Liu Y. LARP7 alleviates psoriasis symptoms in mice by regulating the SIRT1/NF-kappaB signaling pathway. Allergol Immunopathol (Madr). 2023;51(1):140–5. 10.15586/aei.v51i1.765
13. Guo J, Xue H, Zhong H, Sun W, Zhao S, Meng J, et al. Involvement of LARP7 in activation of SIRT1 to inhibit NF-kappaB signaling protects microglia from acrylamide-induced neuroinflammation. Neurotox Res. 2022;40(6):2016–26. 10.1007/s12640-022-00624-1
14. Yan P, Li Z, Xiong J, Geng Z, Wei W, Zhang Y, et al. LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity. Cell Rep. 2021;37(8):110038. 10.1016/j.celrep.2021.110038
15. Wang P, Mo Z, Zhang Y, Guo C, Chikede TK, Chen D, et al. Serum IL-5 levels predict HBsAg seroclearance in patients treated with nucleos(t)ide analogues combined with pegylated interferon. Front Immunol. 2022;13:1104329. 10.3389/fimmu.2022.1104329
16. Xu F, Xu J, Xiong X, Deng Y. Salidroside inhibits MAPK, NF-kappaB, and STAT3 pathways in psoriasis-associated oxidative stress via SIRT1 activation. Redox Rep. 2019;24(1):70–4. 10.1080/13510002.2019.1658377
17. Wang MJ, Huang HJ, Xu YY, Vos H, Gulersonmez C, Stigter E, et al. Metabolic rewiring in keratinocytes by miR-31-5p identifies therapeutic intervention for psoriasis. EMBO Mol Med. 2023;15(4):e15674. 10.15252/emmm.202215674
18. Luan Y, Liu H, Luan Y, Yang Y, Yang J, Ren KD. New insight in HDACs: Potential therapeutic targets for the treatment of atherosclerosis. Front Pharmacol. 2022;13:863677. 10.3389/fphar.2022.863677
19. Zhang G, Xia Z, Tian C, Xia A, You J, Liu J, et al. Discovery of 5-((1H-indazol-3-yl) methylene)-2-thioxoimidazolidin-4-one derivatives as a new class of AHR agonists with anti-psoriasis activity in a mouse model. Bioorg Med Chem Lett. 2023;92:129383. 10.1016/j.bmcl.2023.129383
20. Sui X, Sui Y, Wang Y. LARP7 in papillary thyroid carcinoma induces NIS expression through suppression of the SHH signaling pathway. Mol Med Rep. 2018;17(6):7521–8. 10.3892/mmr.2018.8856
21. Uchikawa E, Natchiar KS, Han X, Proux F, Roblin P, Zhang E, et al. Structural insight into the mechanism of stabilization of the 7SK small nuclear RNA by LARP7. Nucleic Acids Res. 2015;43(6):3373–88. 10.1093/nar/gkv173
22. Stein S, Lohmann C, Schafer N, Hofmann J, Rohrer L, Besler C, et al. SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis. Eur Heart J. 2010;31(18):2301–9. 10.1093/eurheartj/ehq107
Article Sidebar
Published
Nov 1, 2023
Article Details
How to Cite
Li, N., & Liu, Y. (2023). LARP7 upregulates SIRT1 deacetylase activity and inhibits Th1/Th17 cytokine response in psoriatic mice. Allergologia Et Immunopathologia, 51(6), 16-22. https://doi.org/10.15586/v51i6.959
Section
Original Articles
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
Li, N., & Liu, Y. (2023). LARP7 upregulates SIRT1 deacetylase activity and inhibits Th1/Th17 cytokine response in psoriatic mice. Allergologia Et Immunopathologia, 51(6), 16-22. https://doi.org/10.15586/v51i6.959