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.

摘要: Abstract c-Jun N-terminal kinase (JNK) is a critical mitogen activated protein (MAPK) implicated in inflammatory processes, with IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt) being high-affinity JNK inhibitor pronounced anti-inflammatory properties. Here, we studied direct effects of on phenotypical and cytokine-producing characteristics human monocytes/macrophages T cells vitro. Purified monocyte/macrophage were by bacterial lipopolysaccharide (LPS, 1 μg/ml) for 24 h, while particles conjugated antibodies (Abs) against CD2, CD3, CD28 48 h. Treatment (0.5–25 μМ) the presence LPS reduced percentages CD197 (CCR7)-positive macrophage cultures, without affecting CD16+ (FcγRIII, low-affinity Fc-receptor), CD119+ (interferon-γ receptor 1), CD124+ (IL-4 α-subunit) cells. In addition, production tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10 cultures. cell decreased CD25+ numbers both CD4-positive CD4-negative compartments. Central memory СD45RA−/СD197+ effector СD45RA−/СD197- more sensitive to IQ-1S-mediated suppression, as compared naive СD45RA+/СD197+ terminally-differentiated СD45RA+/СD197- also suppressed T-cell cytokine (IL-2, interferon-ɣ, IL-4, IL-10). Collectively, results suggest that could be immediate targets IQ-1S-based immunotherapy. suppressive unlikely associated macrophage/T helper polariation.