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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">cfpd</journal-id><journal-title-group><journal-title xml:lang="ru">Бюллетень физиологии и патологии дыхания</journal-title><trans-title-group xml:lang="en"><trans-title>Bulletin Physiology and Pathology of Respiration</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1998-5029</issn><publisher><publisher-name>Дальневосточный научный центр физиологии и патологии дыхания</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.12737/article_5b96073c5711b1.83866044</article-id><article-id custom-type="elpub" pub-id-type="custom">cfpd-113</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Статьи</subject></subj-group></article-categories><title-group><article-title>ОСОБЕННОСТИ ЭКСПРЕССИИ РЕЦЕПТОРА TRPM8 В РЕСПИРАТОРНОМ ТРАКТЕ БОЛЬНЫХ БРОНХИАЛЬНОЙ АСТМОЙ</article-title><trans-title-group xml:lang="en"><trans-title>PECULIARITIES OF TRPM8 RECEPTOR EXPRESSION IN THE RESPIRATORY TRACT OF ASTHMA PATIENTS</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Наумов</surname><given-names>Д. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Naumov</surname><given-names>D. E.</given-names></name></name-alternatives><email xlink:type="simple">denn1985@bk.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гассан</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Gassan</surname><given-names>D. A.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Килимиченко</surname><given-names>К. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Kilimichenko</surname><given-names>K. F.</given-names></name></name-alternatives><email xlink:type="simple">kolemualnaya@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Афанасьева</surname><given-names>Е. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Afanas'eva</surname><given-names>E. Yu.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шелудько</surname><given-names>Е. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Sheludko</surname><given-names>E. G.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Колосов</surname><given-names>В. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Kolosov</surname><given-names>V. P.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Дальневосточный научный центр физиологии и патологии дыхания</institution></aff><aff xml:lang="en"><institution>Far Eastern Scientific Center of Physiology and Pathology of Respiration</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>18</day><month>11</month><year>2019</year></pub-date><volume>0</volume><issue>69</issue><fpage>19</fpage><lpage>24</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Наумов Д.Е., Гассан Д.А., Килимиченко К.Ф., Афанасьева Е.Ю., Шелудько Е.Г., Колосов В.П., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Наумов Д.Е., Гассан Д.А., Килимиченко К.Ф., Афанасьева Е.Ю., Шелудько Е.Г., Колосов В.П.</copyright-holder><copyright-holder xml:lang="en">Naumov D.E., Gassan D.A., Kilimichenko K.F., Afanas'eva E.Y., Sheludko E.G., Kolosov V.P.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://cfpd.elpub.ru/jour/article/view/113">https://cfpd.elpub.ru/jour/article/view/113</self-uri><abstract><p>Целью настоящего исследования было проанализировать особенности экспрессии рецептора TRPM8 на уровне белка в индуцированной мокроте и назальном эпителии больных бронхиальной астмой (БА), и оценить их взаимосвязь с базисной терапией и холодовой гиперреактивностью дыхательных путей. Было обследовано 43 человека, в том числе лица, больные персистирующей БА легкой и средней тяжести и больные хроническим необструктивным бронхитом (контрольная группа). Анализ экспрессии TRPM8 выполняли методом непрямой проточной цитометрии. Кроме этого, больным проводили спирометрическое исследование и бронхопровокационную пробу с 3-минутной гипервентиляцией холодным воздухом. В результате было установлено, что TRPM8 экспрессирован на макрофагах индуцированной мокроты и назальном эпителии, причем экспрессия среди больных БА, не получавших базисной терапии, выражена в большей степени, по сравнению с больными, получавшими лечение или контрольной группой. Кроме этого, установлена взаимосвязь между повышенным уровнем экспрессии TRPM8 на макрофагах и холодовой гиперреактивностью дыхательных путей. Интерес для дальнейших исследований должно представлять изучение возможности использования TRPM8 как прогностического биомаркера БА на различных этапах развития заболевания.</p></abstract><trans-abstract xml:lang="en"><p>The aim of the study was to analyze the peculiarities of TRPM8 receptor expression at protein level in induced sputum and nasal epithelium of asthma patients, and to evaluate their relationship to maintenance therapy and cold airway hyperresponsiveness. The study enrolled 43 patients, including those with persistent mild-to-moderate asthma and those with chronic non-obstructive bronchitis (control group). Analysis of TRPM8 expression was performed by indirect flow cytometry. In addition, patients underwent spirometry and a bronchoprovocation test with 3-minute cold air hyperventilation. As a result, we found that TRPM8 was expressed on macrophages of induced spleen and nasal epithelium. Its expression in patients with asthma who did not receive maintenance therapy was more pronounced as compared to the treated patients or the control group. Moreover, the relationship between increased expression of TRPM8 on macrophages and cold airway hyperresponsiveness was established. Further studies should reveal the possibility of TRPM8 usage as a prognostic biomarker of asthma at various stages of the disease development.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>бронхиальная астма</kwd><kwd>экспрессия</kwd><kwd>проточная цитометрия</kwd><kwd>холодовая гиперреактивность дыхательных путей</kwd><kwd>базисная терапия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>TRPM8</kwd><kwd>asthma</kwd><kwd>TRPM8</kwd><kwd>expression</kwd><kwd>flow cytometry</kwd><kwd>cold airway hyperresponsiveness</kwd><kwd>maintenance therapy</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Asuthkar S., Demirkhanyan L., Sun X., Elustondo P.A., Krishnan V., Baskaran P., Velpula K.K., Thyagarajan B., Pavlov E.V., Zakharian E. The TRPM8 protein is a testosterone receptor: II. Functional evidence for an ionotropic effect of testosterone on TRPM8 // J. Biol. Chem. 2015. Vol.290, №5. P.2670-2688.</mixed-citation><mixed-citation xml:lang="en">Asuthkar S., Demirkhanyan L., Sun X., Elustondo P.A., Krishnan V., Baskaran P., Velpula K.K., Thyagarajan B., Pavlov E.V., Zakharian E. The TRPM8 protein is a testosterone receptor: II. Functional evidence for an ionotropic effect of testosterone on TRPM8 // J. Biol. Chem. 2015. Vol.290, №5. P.2670-2688.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Asuthkar S., Velpula K.K., Elustondo P.A., Demirkhanyan L., Zakharian E. TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells // Oncotarget. 2015. Vol.6, №19. P.17221-17236.</mixed-citation><mixed-citation xml:lang="en">Asuthkar S., Velpula K.K., Elustondo P.A., Demirkhanyan L., Zakharian E. TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells // Oncotarget. 2015. Vol.6, №19. P.17221-17236.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Behrendt H.J., Germann T., Gillen C., Hatt H., Jostock R. Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay // Br. J. Pharmacol. 2004. Vol.141, №4. P.737-745.</mixed-citation><mixed-citation xml:lang="en">Behrendt H.J., Germann T., Gillen C., Hatt H., Jostock R. Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay // Br. J. Pharmacol. 2004. Vol.141, №4. P.737-745.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Cheon D.Y., Kim J.H., Jang Y.S., Hwang Y.I., Park S., Kim D.G., Jang S.H., Jung K.S. The activation of transient receptor potential melastatin 8 (TRPM8) receptors of bronchial epithelial cells induces airway inflammation in bronchial asthma // Eur. Respir. J. 2016. Vol.48. PA3997.</mixed-citation><mixed-citation xml:lang="en">Cheon D.Y., Kim J.H., Jang Y.S., Hwang Y.I., Park S., Kim D.G., Jang S.H., Jung K.S. The activation of transient receptor potential melastatin 8 (TRPM8) receptors of bronchial epithelial cells induces airway inflammation in bronchial asthma // Eur. Respir. J. 2016. Vol.48. PA3997.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Khalil M., Babes A., Lakra R., Försch S., Reeh P.W., Wirtz S., Becker C., Neurath M.F., Engel M.A. Transient receptor potential melastatin 8 ion channel in macrophages modulates colitis through a balance-shift in TNF-alpha and interleukin-10 production // Mucosal Immunol. 2016. Vol.9, №6. P.1500-1513.</mixed-citation><mixed-citation xml:lang="en">Khalil M., Babes A., Lakra R., Försch S., Reeh P.W., Wirtz S., Becker C., Neurath M.F., Engel M.A. Transient receptor potential melastatin 8 ion channel in macrophages modulates colitis through a balance-shift in TNF-alpha and interleukin-10 production // Mucosal Immunol. 2016. Vol.9, №6. P.1500-1513.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Lamb J.G., Romero E.G., Lu Z., Marcus S.K., Peterson H.C., Veranth J.M., Deering-Rice C.E., Reilly C.A. Activation of Human Transient Receptor Potential Melastatin-8 (TRPM8) by Calcium-Rich Particulate Materials and Effects on Human Lung Cells // Mol. Pharmacol. 2017. Vol.92, №6. P.653-664.</mixed-citation><mixed-citation xml:lang="en">Lamb J.G., Romero E.G., Lu Z., Marcus S.K., Peterson H.C., Veranth J.M., Deering-Rice C.E., Reilly C.A. Activation of Human Transient Receptor Potential Melastatin-8 (TRPM8) by Calcium-Rich Particulate Materials and Effects on Human Lung Cells // Mol. Pharmacol. 2017. Vol.92, №6. P.653-664.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Li M., Li Q., Yang G., Kolosov V.P., Perelman J.M., Zhou X.D. Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism // J. Allergy Clin. Immunol. 2011. Vol.128, №3. P.626-634.</mixed-citation><mixed-citation xml:lang="en">Li M., Li Q., Yang G., Kolosov V.P., Perelman J.M., Zhou X.D. Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism // J. Allergy Clin. Immunol. 2011. Vol.128, №3. P.626-634.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Lin A.H., Liu M.H., Ko H.B., Perng D.W., Lee T.S., Kou Y.R. Inflammatory Effects of Menthol vs. Non-menthol Cigarette Smoke Extract on Human Lung Epithelial Cells: A Double-Hit on TRPM8 by Reactive Oxygen Species and Menthol // Front. Physiol. 2017. Vol.27, №8. P.263.</mixed-citation><mixed-citation xml:lang="en">Lin A.H., Liu M.H., Ko H.B., Perng D.W., Lee T.S., Kou Y.R. Inflammatory Effects of Menthol vs. Non-menthol Cigarette Smoke Extract on Human Lung Epithelial Cells: A Double-Hit on TRPM8 by Reactive Oxygen Species and Menthol // Front. Physiol. 2017. Vol.27, №8. P.263.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Liu H., Liu Q., Hua L., Pan J. Inhibition of transient receptor potential melastatin 8 alleviates airway inflammation and remodeling in a murine model of asthma with cold air stimulus // Acta Biochim. Biophys. Sin. (Shanghai) 2018; Vol.50, №5. P.499-506.</mixed-citation><mixed-citation xml:lang="en">Liu H., Liu Q., Hua L., Pan J. Inhibition of transient receptor potential melastatin 8 alleviates airway inflammation and remodeling in a murine model of asthma with cold air stimulus // Acta Biochim. Biophys. Sin. (Shanghai) 2018; Vol.50, №5. P.499-506.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Liu S.C., Lu H.H., Fan H.C., Wang H.W., Chen H.K., Lee F.P., Yu C.J., Chu Y.H. The identification of the TRPM8 channel on primary culture of human nasal epithelial cells and its response to cooling // Medicine (Baltimore). 2017. Vol.96, №31. e7640.</mixed-citation><mixed-citation xml:lang="en">Liu S.C., Lu H.H., Fan H.C., Wang H.W., Chen H.K., Lee F.P., Yu C.J., Chu Y.H. The identification of the TRPM8 channel on primary culture of human nasal epithelial cells and its response to cooling // Medicine (Baltimore). 2017. Vol.96, №31. e7640.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Nilius B., Owsianik G., Voets T., Peters J.A. Transient receptor potential cation channels in disease // Physiol. Rev. 2007. Vol.87, №1. P.165-217.</mixed-citation><mixed-citation xml:lang="en">Nilius B., Owsianik G., Voets T., Peters J.A. Transient receptor potential cation channels in disease // Physiol. Rev. 2007. Vol.87, №1. P.165-217.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Plevkova J., Kollarik M., Poliacek I., Brozmanova M., Surdenikova L., Tatar M., Mori N., Canning B.J. The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol // J. Appl. Physiol. (1985). 2013. Vol.115, №2. P.268-274.</mixed-citation><mixed-citation xml:lang="en">Plevkova J., Kollarik M., Poliacek I., Brozmanova M., Surdenikova L., Tatar M., Mori N., Canning B.J. The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol // J. Appl. Physiol. (1985). 2013. Vol.115, №2. P.268-274.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Quallo T., Vastani N., Horridge E., Gentry C., Parra A., Moss S., Viana F., Belmonte C., Andersson D.A., Bevan S. TRPM8 is a neuronal osmosensor that regulates eye blinking in mice // Nat. Commun. 2015. Vol.22, №6. P.7150.</mixed-citation><mixed-citation xml:lang="en">Quallo T., Vastani N., Horridge E., Gentry C., Parra A., Moss S., Viana F., Belmonte C., Andersson D.A., Bevan S. TRPM8 is a neuronal osmosensor that regulates eye blinking in mice // Nat. Commun. 2015. Vol.22, №6. P.7150.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Sabnis A.S., Reilly C.A., Veranth J.M., Yost G.S. Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures // Am. J. Physiol. Lung Cell. Mol. Physiol. 2008. Vol.295, №1. P.L194-200.</mixed-citation><mixed-citation xml:lang="en">Sabnis A.S., Reilly C.A., Veranth J.M., Yost G.S. Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures // Am. J. Physiol. Lung Cell. Mol. Physiol. 2008. Vol.295, №1. P.L194-200.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Sabnis A.S., Shadid M., Yost G.S., Reilly C.A. Human lung epithelial cells express a functional cold-sensing TRPM8 variant // Am. J. Respir. Cell Mol. Biol. 2008. Vol.39, №4. P.466-474.</mixed-citation><mixed-citation xml:lang="en">Sabnis A.S., Shadid M., Yost G.S., Reilly C.A. Human lung epithelial cells express a functional cold-sensing TRPM8 variant // Am. J. Respir. Cell Mol. Biol. 2008. Vol.39, №4. P.466-474.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Xing H., Ling J.X., Chen M., Johnson R.D., Tominaga M., Wang C.Y., Gu J. TRPM8 mechanism of autonomic nerve response to cold in respiratory airway // Mol. Pain. 2008. №4. P.22.</mixed-citation><mixed-citation xml:lang="en">Xing H., Ling J.X., Chen M., Johnson R.D., Tominaga M., Wang C.Y., Gu J. TRPM8 mechanism of autonomic nerve response to cold in respiratory airway // Mol. Pain. 2008. №4. P.22.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
