cfpdБюллетень физиологии и патологии дыханияBulletin Physiology and Pathology of Respiration1998-5029Дальневосточный научный центр физиологии и патологии дыхания10.36604/1998-5029-2025-98-94-108cfpd-1298Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHКапсаицин-индуцированная транскриптомная перестройка макрофагов моноцитарного происхождения в процессе дифференцировки in vitroCapsaicin-induced transcriptomic reprogramming of monocyte-derived macrophages during in vitro differentiationНаумовД. Е.NaumovD. E.

Денис Евгеньевич Наумов, канд. мед. наук, зав. лабораторией молекулярных и трансляционных исследований

675000, г. Благовещенск, ул. Калинина, 22

Denis E. Naumov, PhD (Med.), Head of Laboratory of Molecular and Translational Research

22 Kalinina Str., Blagoveshchensk, 675000

denn1985@bk.ruНекрасоваО. О.NekrasovaO. O.

Олеся Олеговна Некрасова, канд. мед. наук, старший научный сотрудник, лаборатория механизмов вирус-ассоциированных патологий развития

675000, г. Благовещенск, ул. Калинина, 22

Olesya O. Nekrasova, PhD (Med.), Senior Staff Scientist, Laboratory of Mechanisms of Virus-Associated Developmental Pathology

22 Kalinina Str., Blagoveshchensk, 675000

foxy_voxy_on@mail.ruГассанД. А.GassanD. A.

Дина Анатольевна Гассан, канд. мед. наук, зав. лабораторией механизмов вирус-ассоциированных патологий развития

675000, г. Благовещенск, ул. Калинина, 22

Dina A. Gassan, PhD (Med.), Head of Laboratory of Mechanisms of Virus-Associated Developmental Pathology

22 Kalinina Str., Blagoveshchensk, 675000

danishi@mail.ruСугайлоИ. Ю.SugayloI. Yu.

Ивана Юрьевна Сугайло, канд. мед. наук, научный сотрудник, лаборатория молекулярных и трансляционных исследований

675000, г. Благовещенск, ул. Калинина, 22

Ivana Yu. Sugaylo, PhD (Med.), Staff Scientist, Laboratory of Molecular and Translational Research

22 Kalinina Str., Blagoveshchensk, 675000

ivanka_888@mail.ruШелудькоЕ. Г.SheludkoE. G.

Елизавета Григорьевна Шелудько, канд. мед. наук, научный сотрудник, лаборатория молекулярных и трансляционных исследований

675000, г. Благовещенск, ул. Калинина, 22

Elizaveta G. Sheludko, PhD (Med.), Staff Scientist, Laboratory of Molecular and Translational Research

22 Kalinina Str., Blagoveshchensk, 675000

liza.sheludko@mail.ruФедеральное государственное бюджетное научное учреждение «Дальневосточный научный центр физиологии и патологии дыхания»Far Eastern Scientific Center of Physiology and Pathology of Respiration20252312202509894108Copyright © Наумов Д.Е., Некрасова О.О., Гассан Д.А., Сугайло И.Ю., Шелудько Е.Г., 20252025Наумов Д.Е., Некрасова О.О., Гассан Д.А., Сугайло И.Ю., Шелудько Е.Г.Naumov D.E., Nekrasova O.O., Gassan D.A., Sugaylo I.Y., Sheludko E.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cfpd.elpub.ru/jour/article/view/1298

Введение. Известно, что каналы с транзиторным рецепторным потенциалом V1 (TRPV1) способны активироваться компонентами сигаретного дыма, пылевыми частицами и активными формами кислорода, а их экспрессия увеличена в альвеолярных макрофагах больных хронической обструктивной болезнью легких (ХОБЛ).Цель. Проанализировать особенности транскриптомного профиля макрофагов, дифференцирующихся из моноцитов периферической крови in vitro на фоне пролонгированного воздействия агониста TRPV1 – капсаицина.Материалы и методы. Моноциты получали из периферической крови пяти практически здоровых добровольцев мужского пола (52,2 ± 3,89 лет). Клетки дифференцировали в течение 10 дней в среде RPMI-1640 (10% эмбриональной телячьей сыворотки, 1% пенициллина/стрептомицина), содержащей 50 нг/мл гранулоцитарно-макрофагального колониестимулирующего фактора (GM-CSF), либо GM-CSF в той же концентрации и капсаицин 50 мкМ. После окончания дифференцировки из полученных макрофагов выделяли тотальную РНК, обогащали мРНК и проводили секвенирование на платформе MGISEQ-200 в режиме SE50. Обработка данных включала картирование прочтений (Salmon), анализ дифференциальной экспрессии (DESeq2) и функционального обогащения генов (Cytoscape). Дополнительно была проведена оценка фенотипа макрофагов с помощью платформы MacSpectrum.Результаты. Дифференцировка макрофагов в присутствии капсаицина сопровождалась, прежде всего, признаками активизации процессов трансляции и транспорта белков, метаболизма липидов и поддержания репликативного потенциала. При этом наблюдалось подавление биологических процессов, связанных с цитокиновым сигналингом, ответом на патогены, способностью стимулировать активацию и пролиферацию лейкоцитов, а также организацией цитоскелета и клеточной подвижностью. Анализ с использованием MacSpectrum показал снижение индексов поляризации (MPI) и дифференцировки (AMDI) у макрофагов, дифференцированных в присутствии капсаицина, что могло свидетельствовать о торможении формирования зрелого провоспалительного фенотипа и развитии гипореактивного, M0-подобного состояния.Заключение. Капсаицин, вероятно, опосредуя свой эффект преимущественно через TRPV1, оказывает существенное влияние на дифференцировку макрофагов, приводя к формированию гипореактивных, не полностью дифференцированных клеток, по ряду характеристик сходных с альвеолярными макрофагами, обнаруживаемыми в дыхательных путях больных ХОБЛ. Полученные данные позволяют рассматривать TRPV1-зависимую модуляцию макрофагов как один из возможных патогенетических механизмов данного заболевания.

Introduction. TRPV1 cation channels are known to be activated by cigarette smoke components, particulate matter, and reactive oxygen species, and their expression is increased in alveolar macrophages of patients with chronic obstructive pulmonary disease (COPD).Aim. To analyze the features of the transcriptome profile of macrophages differentiating from peripheral blood monocytes in vitro under prolonged exposure to the TRPV1 agonist capsaicin.Materials and methods. Monocytes were isolated from the peripheral blood of five apparently healthy male volunteers (52.2±3.89 years). The cells were differentiated for 10 days in RPMI-1640 medium (10% FCS, 1% penicillin/streptomycin) containing 50 ng/ml GM-CSF or GM-CSF at the same concentration and 50 μM capsaicin. Upon completion of differentiation, total RNA was extracted from the resulting macrophages, mRNA was enriched, and sequencing was performed on the MGISEQ-200 platform in SE50 mode. Data processing included read mapping (Salmon), differential expression analysis (DESeq2), and functional gene enrichment (Cytoscape). In addition, macrophage phenotype was assessed using the MacSpectrum platform.Results. Macrophage differentiation in the presence of capsaicin was primarily accompanied by signs of activation of protein translation and transport processes, lipid metabolism, and maintenance of replicative potential. At the same time, suppression of biological processes associated with cytokine signaling, response to pathogens, ability to stimulate leukocyte activation and proliferation, as well as cytoskeletal organization and cell motility was observed. Analysis using MacSpectrum revealed a decrease in the polarization index (MPI) and differentiation index (AMDI) in macrophages differentiated in the presence of capsaicin, indicating inhibition of the development of a mature pro-inflammatory phenotype and the emegrence of a hyporesponsive, M0-like state.Conclusion. Capsaicin, likely mediating its effect primarily through TRPV1, significantly influences macrophage differentiation, leading to the formation of hyporesponsive, incompletely differentiated cells that share several characteristics with alveolar macrophages found in the airways of COPD patients. These data suggest TRPV1-dependent modulation of macrophages as a possible pathogenetic mechanism contributing to this disease.

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The authors declare that there are no conflicts of interest present.