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

c-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.