Role of Cxcr3 Chemokine Receptor and Its Ligands in Certain Diseases

Арсентьева, Н. А.; Семенов, А В; Жебрун, Д. А.; Васильева, Е. В.; Тотолян, Арег А.

doi:10.15789/1563-0625-2019-4-617-632

Cited by 6 publications

(1 citation statement)

References 96 publications

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“…Показано их участие в процессах фиброгенеза печени. Например, была подтверждена важная роль лигандов CXCR3 в иммунопатогенезе хронического вирусного гепатита С: концентрация этих хемокинов значительно возрастает и имеет прямую связь со степенью фиброза печени [2,10,50]. Повышенные уровни CXCL10/IP-10 в плазме связывают с фиброзом печени, тогда как уровни CXCL9/MIG, согласно некоторым исследованиям, в основном ассоциированы с воспалением [49].…”

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Analysis of blood plasma cytokine profile in healthy residents of the Republic of Guinea

et al. 2020

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The cytokine system is a large group of humoral factors produced by immune cells and involved in the pathogenesis of most human diseases. To assess the significance of changes in cytokines/chemokines under pathological conditions, appropriate reference values are required for healthy people. As known from existing literature, most studies of various cytokine/chemokine concentrations in blood plasma were performed in healthy subjects from Western Europe and North America. Certain inter-population differences are known, with respect to production of distinct cytokines in different racial and national groups. Only single studies concern normal levels of distinct cytokines in blood plasma of healthy African residents. The purpose of this study was to determine the blood plasma cytokine profile in healthy residents of the Republic of Guinea (RG), and to establish normal cytokine values.We have examined 24 healthy RG residents and 23 residents of St. Petersburg. Concentrations of 40 cytokines/chemokines were determined in blood plasma. The study was performed using multiplex analysis by xMAP technology.The following cytokine/chemokine levels were significantly increased in the blood plasma of the RG residents: IFNγ, IL-2, IL-4, IL-6, IL-10, TNFα, CCL1/I-309, CCL3/MIP-1α, CCL7/MCP-3, CCL17/ TARC, CCL19/MIP-3β, CCL20/MIP-3α, CCL21/6Ckine, CXCL2/Gro-β, CXCL5/ENA-78, CXCL6/ GCP-2, CXCL9/MiG, CX3CL1/Fractalkine (р < 0.001). For the CCL8/MCP-2, CCL22/MDC, CXCL1/ Gro-α and CXCL12/SDF-1α+β chemokines a trend for increased concentration was revealed, in comparison with residents of St. Petersburg (р < 0.05). Moreover, the levels of CCL23/MPIF-1 and MIF were significantly lower (р < 0.0001) in the RG residents. There was a tendency for decreased levels (р < 0.05) for CCL2/MCP-1 and CCL24/Eotaxin-2 chemokines in blood plasma taken from RG residents. There were no differences in levels of cytokines/chemokines for the studied groups: GM-CSF, IL-1β, IL-16, CCL11/Eotaxin, CCL13/MCP-4, CCL15/Leukotactin-1, CCL25/TECK, CCL26/Eotaxin-3, CCL27/CTACK, CXCL8/IL-8, CXCL10/IP-10, CXCL11/I-TAC, CXCL13/BCA, and CXCL16/SCYB16. Hence, this study has presented for the first time the normal limits for a wide range of cytokines/chemokines in blood plasma of the African inhabitants. Interpopulation differences were found, including those for constitutive chemokines. Different levels of CCL19/ MIP-3β and CCL21/6Ckine chemokines (the CCR7 receptor ligands) for the two populations may indirectly indicate the physiological features of T-cell maturation. Increased levels of CXCR2 receptor ligands in the blood plasma of Guineans, i.e., CXCL2/Gro-β, CXCL5/ENA-78 and CXCL6/GCP-2, may be due to additional function of these chemokines as ligands for atypical DARC chemokine receptor, which neutralizes chemokines from the blood flow, whereas 95% of West Africans have mutations in the DARC gene and do not express this receptor. Increased levels of proinflammatory IL-6 and TNFα cytokines, and chemokine CCL20/MIP-3α in blood plasma from RG residents may suggest inflammatory processes in the liver, since 100% of the examined Guineans had antibodies against the hepatitis A virus, 48% had antibodies to hepatitis B virus (anti-HBs), and 12% had antibodies against hepatitis C virus. In summary, the differences in cytokine/chemokine level may be related to specific environment, circulation of infectious diseases, composition of intestinal, skin and mucosal microbiota, as well as distinct genetic features.

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Section: Introductionunclassified

Analysis of blood plasma cytokine profile in healthy residents of the Republic of Guinea

et al. 2020

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CXCR3 chemokine receptor ligands in sarcoidosis

et al. 2021

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Sarcoidosis is a polysystemic inflammatory disease of unknown etiology, morphologically related to the group of granulomatosis, with heterogeneous clinical manifestations and outcomes. Immune cells, in particular T helper cells, are attracted to lung tissue and/or other organs by chemokine gradients and play an important role in the granuloma formation. T helper cells migrate from peripheral blood to the tissues due to expression of CXCR3 chemokine receptor on their surface. It interacts, e.g., with CXCL9/MIG, CXCL10/IP- 10, and CXCL11/I-TAC. Our study was aimed for determining the levels of CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC chemokines in peripheral blood of the patients with sarcoidosis, depending on the features of their clinical course before administration of immunosuppressive therapy. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 52). In 37% (19/52), they exhibited acute clinical manifestations, and 63% (33/52) had chronic sarcoidosis. The control group included peripheral blood samples from healthy volunteers (n = 22). The chemokine concentrations (pg/ml) were determined by multiplex analysis using xMAP technology (Luminex), and Milliplex MAP test system (Millipore, USA). In the patients with sarcoidosis, significantly higher levels of chemokines were shown relative to healthy volunteers: CXCL9, 4013.00 pg/ml vs 1142.00 pg/ml (p < 0.001); CXCL10, 565.90 pg/ml vs 196.60 pg/ml (p < 0.001); CXCL11, 230.20 pg/ml vs 121.10 pg/ml (p = 0.018). Plasma concentrations of CXCL9 and CXCL10 were significantly increased both in blood samples from patients with acute and chronic sarcoidosis compared to healthy volunteers, p < 0.001. The level of CXCL11 chemokine was significantly increased only in the patients with chronic sarcoidosis, compared to the healthy volunteers: respectively, 251.50 pg/ml and 121.10 pg/ml (p = 0.044). The levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), with r = 0.374; p = 0.042. The ACE level in sarcoidosis is considered a clinical and laboratory index of the disease activity. In acute sarcoidosis, the level of CXCL11 chemokine was not significantly higher than in healthy individuals, whereas the CXCL9 chemokine content was significantly increased and correlated with ACE activity (r = 0.762; p = 0.037). The level of CXCL9 chemokine was significantly decreased in patients with signs of fibrosis as compared with fibrosis-free patients (1839.88 pg/ml vs 4375.52 pg/ml, p = 0.035). Significantly higher levels of CXCL9 were detected in cases of systemic sarcoidosis, i.e. 6036.84 pg/ml, as compared with 1927.44 pg/ml in the patients without these signs (p = 0.018). Evaluation of clinical and laboratory diagnostic characteristics for plasma chemokine levels in sarcoidosis patients allowed to assess their sensitivity and specificity. The respective values were as follows: in acute sarcoidosis: for CXCL9, 84% and 95%; for CXCL10, 84% and 95%; for CXCL11, 74% and 59%. In chronic sarcoidosis, the respective values for CXCL9 were 82% and 72%; for CXCL10, 91% and 77%; for CXCL11, 79% and 55%, respectively. Thus, the determination of plasma CXCL9, CXCL10, and CXCL11 chemokines in sarcoidosis allows of understanding their role in development of the disease, e.g., recruitment of T helper cells from peripheral blood to the lung tissue, and granuloma formation. Clinical and immunological comparisons of CXCL9 levels in the peripheral blood of patients and characteristics of the clinical course of sarcoidosis indicate to the role of this diagnostic parameter for assessing the disease activity, signs of lung fibrosis, and systemic manifestations in this disease.

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Content of certain cytokines and chemokines in blood ofpatients with chronic hepatitis B in the early stages of liver fibrosis

Batsunov¹,

Арсентьева²,

Любимова³

et al. 2020

Med. immunol.

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Batsunov O.K. et al. Бацунов О.К. и др. Medical Immunology (Russia)/Meditsinskaya Immunologiya Медицинская Иммунология содержанием TNFα и хемокинов CCL2/MCP-1 и CCL8/MCP-2, чего не наблюдается в контрольной группе. В то же время в контрольной группе обнаружена корреляция между содержанием TNFα и хемокина CXCL9/MIG, что не выявлено в группе больных. Для обеих групп обнаружена корреляция между содержанием хемокинов CXCL9/MIG и CXCL10/IP-10. На основании данных исследования разработан алгоритм, который позволяет установить в качестве причины развития начальной формы фиброза F0-F1 хронический гепатит В либо хронический гепатит С по содержанию в плазме крови цитокинов IFNγ, ССL2/MCP-1 и CCL8/MCP-2 с диагностической эффективностью 89,4%.

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Role of Cxcr3 Chemokine Receptor and Its Ligands in Certain Diseases

Cited by 6 publications

References 96 publications

Analysis of blood plasma cytokine profile in healthy residents of the Republic of Guinea

Analysis of blood plasma cytokine profile in healthy residents of the Republic of Guinea

CXCR3 chemokine receptor ligands in sarcoidosis

Content of certain cytokines and chemokines in blood ofpatients with chronic hepatitis B in the early stages of liver fibrosis

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