Inhibitory effect of IQ-1S, a selective c-Jun N-terminal kinase (JNK) inhibitor, on phenotypical and cytokine-producing characteristics in human macrophages and T-cells

dc.contributor.authorSeledtsov, Victor I.
dc.contributor.authorMalashchenko, Vladimir V.
dc.contributor.authorMeniailo, Maksim E.
dc.contributor.authorAtochin, Dmitriy N.
dc.contributor.authorSeledtsova, Galina V.
dc.contributor.authorSchepetkin, Igor A.
dc.date.accessioned2021-11-02T19:12:45Z
dc.date.available2021-11-02T19:12:45Z
dc.date.issued2020-07
dc.description.abstractc-Jun N-terminal kinase (JNK) is a critical mitogen activated protein kinase (MAPK) implicated in inflammatory processes, with IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt) being a high-affinity JNK inhibitor with pronounced anti-inflammatory properties. Here, we studied direct effects of IQ-1S on phenotypical and cytokine-producing characteristics of activated human monocytes/macrophages and T cells in vitro. Purified monocyte/macrophage cells were activated by bacterial lipopolysaccharide (LPS, 1 μg/ml) for 24 h, while T cells were activated by particles conjugated with antibodies (Abs) against human CD2, CD3, and CD28 for 48 h. Treatment with IQ-1S (0.5–25 μМ) in the presence of LPS reduced percentages of CD197 (CCR7)-positive cells in macrophage cultures, without affecting CD16+ (FcγRIII, low-affinity Fc-receptor), CD119+ (interferon-γ receptor 1), and CD124+ (IL-4 receptor α-subunit) cells. In addition, IQ-1S reduced production of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in macrophage cultures. In activated T cell cultures, IQ-1S decreased CD25+ cell numbers in both CD4-positive and CD4-negative T cell compartments. Central memory СD45RA−/СD197+ and effector memory СD45RA−/СD197- T cells were more sensitive to IQ-1S-mediated suppression, as compared to naïve СD45RA+/СD197+ and terminally-differentiated effector СD45RA+/СD197- T cells. IQ-1S also suppressed T-cell cytokine production (IL-2, interferon-ɣ, IL-4, and IL-10). Collectively, the results suggest that both human macrophage and T cells could be immediate cell targets for IQ-1S-based anti-inflammatory immunotherapy. IQ-1S-mediated suppressive effects were unlikely to be associated with macrophage/T helper polariation.en_US
dc.identifier.citationSeledtsov, Victor I., Vladimir V. Malashchenko, Maksim E. Meniailo, Dmitriy N. Atochin, Galina V. Seledtsova, and Igor A. Schepetkin. “Inhibitory Effect of IQ-1S, a Selective c-Jun N-Terminal Kinase (JNK) Inhibitor, on Phenotypical and Cytokine-Producing Characteristics in Human Macrophages and T-Cells.” European Journal of Pharmacology 878 (July 2020): 173116. doi:10.1016/j.ejphar.2020.173116.en_US
dc.identifier.issn0014-2999
dc.identifier.urihttps://scholarworks.montana.edu/handle/1/16524
dc.language.isoen_USen_US
dc.rights© This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0en_US
dc.titleInhibitory effect of IQ-1S, a selective c-Jun N-terminal kinase (JNK) inhibitor, on phenotypical and cytokine-producing characteristics in human macrophages and T-cellsen_US
dc.typeArticleen_US
mus.citation.extentfirstpage173116en_US
mus.citation.journaltitleEuropean Journal of Pharmacologyen_US
mus.citation.volume878en_US
mus.data.thumbpage3en_US
mus.identifier.doi10.1016/j.ejphar.2020.173116en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US

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