Extracellular vesicles secreted by the ТНР-1 cells influence on the inflammation gene expression in zebrafish

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

Extracellular vesicles secreted by immune cells may play a significant role in the initiation, maintenance, and progression of systemic inflammation. The aim of the study was to investigate the regulatory effect of extracellular vesicles (EVs) produced by activated monocyte-like THP-1 cells on expression levels of inflammatory genes in a zebrafish. Real-time PCR analysis was performed to investigate the relative expression levels of il-1β, il-6, tnf-α, ifn-γ, mpeg1.1, mpeg1.2, mpx, and il-10 genes in the brain, liver, and heart of zebrafish followed by intracelomic injection of EVs produced by THP-1 cells activated with tumor necrosis factor (TNF) and phorbol-12-myristate-13-acetate (PMA) at different concentrations. EVs, secreted by activated THP-1 cells with TNF at a concentration of 10 ng/mL and PMA at concentrations of 16 and 50 ng/mL, reduced the expression levels of il-1β, ifn-γ, tnf-α, mpx, mpeg1.1, mpeg1.2, and IL-10 genes in the brain, heart and liver of Danio rerio. Wherein, EVs secreted by THP-1 cells treated with TNF at doses of 10 and 20 ng/ml had opposite effects on the gene expression levels of il-1β in the brain, il-1β, il-10, and il-6 in the heart; on il-1β, il-10, mpx, and mpeg1.2 in the liver. EVs secreted by THP-1 cells treated with PMA at doses of 16 and 50 ng/ml had opposite effects on the expression levels of il-6 and il-10 genes in the heart and ifn-γ gene in the liver. EVs, produced by activated THP-1 cells have a systemic effect on Danio rerio manifested in a changing of the expression level of pro- and anti-inflammatory cytokine genes in the brain, liver, and heart. The qualitative composition of the EVs produced by activate THP-1 cells varies depending on the type and dose of the used stimulus, that reflects on strength and direction of the effects detected in vivo.

Толық мәтін

Рұқсат жабық

Авторлар туралы

D. Sambur

Institution “Almazov National Medical Research Center”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg

O. Kalinina

Institution “Almazov National Medical Research Center”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg

A. Aquino

Institution “Almazov National Medical Research Center”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg

P. Tirikova

Institution “Almazov National Medical Research Center”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg

M. Migunova

Institution “Almazov National Medical Research Center”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg

E. Koroleva

Institution “Almazov National Medical Research Center”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg

A. Trulyov

Institution “Institute of Experimental Medicine”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg

A. Rubinshtein

Institution “Almazov National Medical Research Center”; Institution “Institute of Experimental Medicine”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg; St. Petersburg

I. Kudryavtsev

Institution “Almazov National Medical Research Center”; Institution “Institute of Experimental Medicine”

Email: golovkin_a@mail.ru
Ресей, St. Petersburg; St. Petersburg

A. Golovkin

Institution “Almazov National Medical Research Center”

Хат алмасуға жауапты Автор.
Email: golovkin_a@mail.ru
Ресей, St. Petersburg

Әдебиет тізімі

  1. Lenz A., Franklin G.A., Cheadle W.G. // Systemic inflammation after trauma / Injury. 2007. V. 38. № 12. P. 1336–1345.
  2. Lee O., Xinyi Z., Partha D. // Pharmacological research. 2021. V. 170. P. 105692.
  3. Головкин А.С. Механизмы синдрома системного воспалительного ответа после операций с применением искусственного кровообращения / Дис… доктора мед. наук. 2014. Т. 14. № 03.
  4. Abbas A., Lichtman A., Pillai S. // Cellular and Molecular Immunology 9th edition. 2018. P. 62–65.
  5. Козлов В.А., Тихонова Е.П., Савченко А.А., Кудрявцев И.В., Андронова Н.В., Анисимова Е.Н., Головкин А.С., Демина Д.В., Здзитовецкий Д.Э., Калинина Ю.С., Каспаров Э.В., Козлов И.Г., Корсунский И.А., Кудлай Д.А., Кузьмина Т.Ю., Миноранская Н.С., Продеус А.П., Старикова Э.А., Черданцев Д.В., Чесноков А.Б., Шестерня П.А., Борисов А.Г. // Клиническая иммунология. Практическое пособие для инфекционистов. 2021. 550 с.
  6. Каспаров Э.В., Савченко А.А., Кудлай Д.А., Кудрявцев И.В., Тихонова Е.П., Головкин А.С., Борисов А.Г. // Клиническая иммунология. Реабилитация иммунной системы. 2022. 196 с.
  7. Черешнев В.А., Гусев Е.Ю. // Медицинская иммунология. 2012. Т. 14. № 1–2. С. 9–20.
  8. Cavaillon J.M., Annane D. // Journal of endotoxin research. 2006. V. 12. № 3. P. 151–170.
  9. Chanput W., Mes J., Vreeburg R.A., Savelkoul H.F., Wichers H.J. // Food & function. 2010. V. 1. № 3. P. 254–261.
  10. Zhang Y., Liu D., Chen X., Li J., Li L., Bian Z., Sun F., Lu J., Yin Y., Cai X., Sun Q., Wang K., Ba Y., Wang Q., Wang D., Yang J., Liu P., Xu T., Yan Q., Zhang J., Zen K., Zhang C.Y. // Molecular cell. 2010. V. 39. № 1. P. 133–144.
  11. McDonald M.K., Tian Y., Qureshi R.A., Gormley M., Ertel A., Gao R., Aradillas Lopez E., Alexander M., Sacan A., Fortina P., Ajit S.K. // Pain. 2014. V. 155. № 8. P. 1527–1539.
  12. Genin M., Clement F., Fattaccioli A., Raes M., Michiels C. // BMC Cancer. 2015. V. 15. № 1. P. 1–14.
  13. Chanput W., Mes J., Savelkoul H.F., Wichers H.J. // Food & function. 2013. V. 4. № 2. P. 266–276.
  14. Walsh S.A., Davis T.A. // Journal of Inflammation. 2022. V. 19. № 1. P. 6.
  15. Rossaint J., Kühne K., Skupski J., Van Aken H., Looney M.R., Hidalgo A., Zarbock A. // Nature communications. 2016. V. 7. № 1. P. 13464.
  16. Ohayon L., Zhang X., Dutta P. // Pharmacological research. 2021. V. 170. P. 105692.
  17. Aires I.D., Ribeiro-Rodrigues T., Boia R., Ferreira-Rodrigues M., Girao H., Ambrosio A.F., Santiago A.R. // Biomolecules. 2021. V. 11. № 6. P. 770.
  18. Hu Q., Su H., Li J., Lyon C., Tang W., Wan M., Hu T.Y. // Precision Clinical Medicine. 2020. V. 3. № 1. P. 54–66.
  19. Doyle L.M., Wang M.Z. // Cells. 2019. V. 8. № 7. P. 727.
  20. Zaborowski M.P., Balaj L., Breakefield X.O., Lai C.P. // Bioscience. 2015. V. 65. № 8. P. 783–797.
  21. Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., Collins J.E., Humphray S., McLaren K., Matthews L. et al. // Nature. 2013. V. 496. № 7446. P. 498–503.
  22. Zizioli D., Mione M., Varinelli M., Malagola M., Bernardi S., Alghisi E., Borsani G., Finazzi D., Monti E., Presta M., Russo D. // Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2019. V. 1865 № 3. P. 620–633.
  23. Baranasic D., Hörtenhuber M., Balwierz P.J., Zehnder T., Mukarram A.K., Nepal C., Várnai C., Hadzhiev Y., Jimenez-Gonzalez A., Li N. et al. // Nature genetics. 2022. V. 54. № 7. P. 1037–1050.
  24. Акино А Д., Рубинштейн А.А., Головкин И.А., Тирикова П.В., Трулев А.С., Кудряыцев И.В., Головкин А.С. // Комплексные проблемы сердечно-сосудистых заболеваний. – 2024. Опубликовано онлайн 07.12.2023
  25. Dubashynskaya N.V., Bokatyi A.N., Golovkin A.S., Kudryavtsev I.V., Serebryakova M.K., Trulioff A.S., Dubrovskii Y.A., Skorik Y.A. // International Journal of Molecular Sciences. 2021. V. 22. № 20. P. 10960.
  26. Kudryavtsev I., Kalinina O., Bezrukikh V., Melnik O., Golovkin A. // Viruses. 2021. V. 13. № 5. P. 767.
  27. Kondratov K., Nikitin Y., Fedorov A., Kostareva A., Mikhailovskii V., Isakov D., Ivanov A., Golovkin A. // Journal of extracellular vesicles. 2020. V. 9. № 1. P. 1743139.
  28. Fedorov A., Kondratov K., Kishenko V., Mikhailovskii V., Kudryavtsev I., Belyakova M., Sidorkevich S., Vavilova T., Kostareva A., Sirotkina O., Golovkin A. // Platelets. 2020. V. 31. № 2. P. 226–235.
  29. Théry C., Witwer K.W., Aikawa E., Alcaraz M.J., Anderson J.D., Andriantsitohaina R., Antoniou A., Arab T., Archer F., Atkin-Smith G.K. et al. // Journal of extracellular vesicles. 2018. V. 7. № 1. P. 1535750.
  30. Welsh J.A., Van Der Pol E., Arkesteijn G.J.A., Bremer M., Brisson A., Coumans F., Dignat-George F., Duggan E., Ghiran I., Giebel B., Görgens A., Hendrix A., Lacroix R., Lannigan J., Libregts SFWM, Lozano-Andrés E., Morales-Kastresana A., Robert S., De Rond L., Tertel T., Tigges J., De Wever O., Yan X., Nieuwland R., Wauben MHM, Nolan J.P., Jones J.C. // Journal of extracellular vesicles. 2020. V. 9. № 1. P. 1713526.
  31. Welsh J.A., Arkesteijn G.J.A., Bremer M., Cimorelli M., Dignat-George F., Giebel B., Görgens A., Hendrix A., Kuiper M., Lacroix R., Lannigan J., van Leeuwen T.G., Lozano-Andrés E., Rao S., Robert S., de Rond L., Tang V.A., Tertel T., Yan X., Wauben M.H.M., Nolan J.P., Jones J.C., Nieuwland R., van der Pol E. // Journal of Extracellular Vesicles. 2023. V. 12. № 2. P. e12299.
  32. Ма И., Федоров А.В., Кондратов К.А., Князева А.А., Васютина М.Л., Головкин А.С. // Медицинская иммунология. 2021. Т. 23. № 5. С. 1069–1078.
  33. Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.D., Coopersmith C.M., Hotchkiss R.S., Levy M.M., Marshall J.C., Martin G.S., Opal S.M., Rubenfeld G.D., van der Poll T., Vincent J.L., Angus D.C. // Jama. 2016. V. 315. № 8. P. 801–810.
  34. Mira J.C., Gentile L.F., Mathias B.J., Efron P.A., Brakenridge S.C., Mohr A.M., Moore F.A., Moldawer L L. // Critical care medicine. 2017. V. 45. № 2. P. 253–262.
  35. Toliver-Kinsky T., Kobayashi M., Suzuki F., Sherwood E.R. // Total burn care. 2018. P. 205–220. e4.
  36. Yáñez-Mó M., Siljander P.R., Andreu Z., Zavec A.B., Borràs F.E., Buzas E.I., Buzas K., Casal E., Cappello F., Carvalho J. et al. // Journal of extracellular vesicles. 2015. V. 4. № 1. P. 27066.
  37. Willekens F.L., Werre J.M., Kruijt J.K., Roerdinkholder-Stoelwinder B., Groenen-Döpp Y.A., van den Bos A.G., Bosman G.J., van Berkel T.J. // Blood. 2005. V. 105. № 5. P. 2141–2145.
  38. Linxweiler J., Kolbinger A., Himbert D., Zeuschner P., Saar M., Stöckle M., Junker K. // Cancers. 2021. V. 13. № 19. P. 4937.
  39. Morad G., Carman C.V., Hagedorn E.J., Perlin J.R., Zon L.I., Mustafaoglu N., Park T.E., Ingber D.E., Daisy C.C., Moses M.A. // ACS nano. 2019. V. 13. № 12. P. 13853–13865.
  40. Banks W.A., Sharma P., Bullock K.M., Hansen K.M., Ludwig N., Whiteside T.L. // International journal of molecular sciences. 2020. V. 21. № 12. P. 4407.
  41. Carata E., Muci M., Simona Di Giulio, Mariano S., Panzarini E. // International Journal of Molecular Sciences. 2023. V. 24. № . 14. P. 11251.
  42. Saint-Pol J., Gosselet F., Duban-Deweer S., Pottiez G., Karamanos Y. // Cells. 2020. V. 9. № 4. P. 851.
  43. Kodidela S., Sinha N., Kumar A., Zhou L., Godse S., Kumar S. // Scientific Reports. 2023. V. 13. № 1. P. 3005.
  44. Vakili S., Ahooyi T.M., Yarandi S.S., Donadoni M., Rappaport J., Sariyer I.K. // Brain sciences. 2020. V. 10. № 7. P. 424.
  45. Sarkar A., Mitra S., Mehta S., Raices R., Wewers M.D. // PloS one. 2009. V. 4. № 9. P. e7140.
  46. Ismail N., Wang Y., Dakhlallah D., Moldovan L., Agarwal K., Batte K., Shah P., Wisler J., Eubank T.D., Tridandapani S., Paulaitis M.E., Piper M.G., Marsh C.B. // Blood. 2013. V. 121. № 6. P. 984–995.
  47. Qu Y., Ramachandra L., Mohr S., Franchi L., Harding C.V., Nunez G., Dubyak G.R. // The Journal of Immunology. 2009. V. 182. № 8. P. 5052–5062.
  48. Femminò S., Penna C., Margarita S., Comità S., Brizzi M.F., Pagliaro P. // Vascular Pharmacology. 2020. V. 135. P. 106790.
  49. Schindler V.E.M., Alhamdan F., Preußer C., Hintz L., Alashkar Alhamwe B., Nist A., Stiewe T., Pogge von Strandmann E., Potaczek D.P., Thölken C., Garn H. // Biomedicines. 2022. V. 10. № 3. P. 622.
  50. Słomka A., Urban S.K., Lukacs-Kornek V., Żekanowska E., Kornek M. // Frontiers in immunology. 2018. V. 9. P. 2723.
  51. Caruso S., Poon I.K.H. // Frontiers in immunology. 2018. V. 9. P. 1486.
  52. Sheikh N.A., Jones L.A. // Cancer Immunology, Immunotherapy. 2008. V. 57. № 9. P. 1381–1390.
  53. Simak J., Gelderman M.P., Yu H., Wright V., Baird A.E. // Journal of thrombosis and haemostasis. 2006. V. 4. № 6. P. 1296–1302.
  54. Lackner P., Dietmann A., Beer R., Fischer M., Broessner G., Helbok R., Schmutzhard E. // Stroke. 2010. V. 41. № 10. P. 2353–2357.
  55. El-Gamal H., Parray A.S., Mir F.A., Shuaib A., Agouni A. // Journal of Cellular Physiology. 2019. V. 234. № 10. P. 16739–16754.

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
2. Fig. 1. Design of the study.

Жүктеу (150KB)
3. Fig. 2. Characteristics of extracellular vesicles secreted by THP-1 cells. The size of extracellular vesicles (a) and dispersion (b), estimated by the results of using the dynamic light scattering method. The results of the Western blot analysis (b) performed with antibodies to heat shock protein 70 (HSP70) and membrane glycoprotein of the tetraspanin family CD9. Designations: V_NA – BB secreted by inactive THP-1 cells; V_PMA2 – BB secreted by THP-1 cells when stimulated by PMA at a concentration of 50 ng/ml; V_TNF2 – BB secreted by THP-1 cells upon TNF stimulation at a concentration of 20 ng/ml; THP-1 total is a cell lysate.

Жүктеу (148KB)
4. Fig. 3. Average sizes and concentrations of explosives secreted by TNR-1 cells, calculated from the analysis of the trajectory of nanoparticles in the ranges of 30-150 and 150-400 nm: a – table size/concentration of extracellular vesicles produced in the range of 30-150 and 150-400 nm; b – graphs size/concentration of explosives secreted by THP-1 cells upon activation TNF and PMA in different concentrations. Designations: V_NA – BB secreted by inactive THP-1 cells; V_PMA1 – BB secreted by THP-1 cells when stimulated by PMA at a concentration of 16 ng/ml; V_PMA2 – BB secreted by THP-1 cells when stimulated by PMA at a concentration of 50 ng/ml; V_TNF1 – BB secreted by THP-1 cells when stimulated by TNF at a concentration of 10 ng/ml; V_TNF2 – BB secreted by THP-1 cells when stimulated by TNF at a concentration of 20 ng/ml.

Жүктеу (236KB)
5. Fig. 4. Immunophenotyping of extracellular vesicles secreted by THP-1 cells, studied by highly sensitive flow laser cytometry. Representative two–parameter pseudo-color graphs of immunophenotyping results - with anti-CD54-PE and Annexin V-FITC antibodies (a); with anti-CD63-APC and anti–CD9-PE/Cy7 antibodies (b); c - concentrations of marker-positive extracellular vesicles. The results are presented in the number of events in mcl, Iu (25; 75). The designations of the groups are similar to Fig. 3.

Жүктеу (530KB)
6. Fig. 5. Relative expression of il-1β (a), il-6 (b), il-10 (c), tnf-α (d), ifn-γ (e), mpx (e), mpeg1.1 (g), mpeg1.2 (h) genes in the brain samples of Danio rerio fish of the studied groups: Control – intact fish; DPBS – injection of DPBS solution; V_NA – injection of explosives secreted by inactive THP-1 cells; V_RMA1 – injection of explosives secreted by THP-1 cells during stimulation of PMA at a concentration of 16 ng/ml; V_RMA2 – injection of explosives secreted by THP cells-1 with stimulation of PMA at a concentration of 50 ng/ml; V_TNF1 – injection of explosives secreted by THP-1 cells with stimulation of TNF at a concentration of 10 ng/ml; V_TNF2 is an injection of explosives secreted by THP–1 cells during TNF stimulation at a concentration of 20 ng/ml.

Жүктеу (258KB)
7. Fig. 6. A heat map of the correlation between the relative gene expression in the brain samples of Danio rerio fish within each study group. Groups of fish with only reliable correlations are presented (p < 0.05): a – e are groups of fish, the designations of which are similar to Fig. 5. The band of the color scale shows the range of the correlation coefficient (r). The red color indicates a high positive correlation, decreasing to a blue band, which represents a negative correlation.

Жүктеу (234KB)
8. Fig. 7. Relative expression of il-1β (a), il-6 (b), il-10 (c), tnf-α (d), ifn-γ (e), mpeg1.1 (e) genes in Danio rerio fish heart samples of the studied groups. Significant differences between the groups at p < 0.05. The designations of the fish groups are similar to Fig. 5.

Жүктеу (220KB)
9. Fig. 8. Heat map of the correlation between gene expression in Danio rerio fish heart samples. The groups of fish with only reliable correlations (p < 0.05) are presented: a – b – groups of fish, the designations of which are similar to Fig. 5. The band of the color scale shows the range of the correlation coefficient (r). The red color indicates a high positive correlation, decreasing to a blue band, which represents a negative correlation.

Жүктеу (121KB)
10. Fig. 9. Relative expression of il-1β (a), il-6 (b), il-10 (c), tnf-α (d), ifn-γ (e), mpx (e), mpeg1.1 (g), mpeg1.2 (h) genes in the liver samples of Danio rerio fish of the studied groups. Significant differences between the groups at p < 0.05. The designations of the fish groups are similar to Fig. 5.

Жүктеу (234KB)
11. Fig. 10. Heat map of the correlation between gene expression in Danio rerio fish liver samples. Groups of fish with only reliable correlations are presented (p < 0.05); a – d are groups of fish whose designations are similar to Fig. 5. The band of the color scale shows the range of the correlation coefficient (r). The red color indicates a high positive correlation, decreasing to a blue band, which represents a negative correlation.

Жүктеу (204KB)

© Russian Academy of Sciences, 2024