Recombinant human IL-26 facilitates the innate immune response to endotoxin in the bronchoalveolar space of mice in vivo

Abstract

Interleukin (IL)-26 is released in response to bacterial endotoxin (LPS) in the bronchoalveolar space of humans in vivo and it may potentiate neutrophil chemotaxis by enhanced IL-26 receptor stimulation. However, the effects of extracellular IL-26 protein on the innate immune response in the lungs in vivo remain unknown. Here, we characterized these effects of IL-26 on a wide range of aspects of the innate immune response to LPS in different compartments of the lungs in vivo over time. We administrated recombinant human (rh) IL-26 protein in the bronchoalveolar space using intranasal instillation in a mouse in vivo model, with and without prior instillation of LPS. We verified gene expression of the IL-26 receptor complex in mouse lungs and observed that, after instillation of LPS, rhIL-26 increases the phosphorylation of STAT3, a signaling molecule of the IL-26 receptor complex. We also observed that rhIL-26 exerted additional stimulatory and inhibitory actions that are compartment- and time-dependent, resulting in alterations of cytokines, proteinases, tissue inflammation and the accumulation of innate effector cells. Without the prior instillation of LPS, rhIL-26 exerted time-dependent effects on total gelatinase activity but few other effects. Most important, after instillation of LPS, rhIL-26 cleared inflammatory cells from local tissue and increased the accumulation of innate effector cells in the bronchoalveolar space. Tentatively, rhIL-26 may facilitate the innate immune response towards the bronchoalveolar space in vivo and represents a potential target for therapy in lung disorders involving the innate immune response.

Interleukin-26, preferentially produced by T H 17 lymphocytes, regulates CNS barrier function

“… 15 Therefore, murine cell lines or mouse models have been used to further unravel the mechanisms of IL-26 and to study the effect of IL-26 in vivo. 15 , 24 , 25 Moreover, the results of these studies were in line with findings obtained in human in vitro experiments. To assess the role of IL-26 in vivo in the context of neuroinflammation, we administered rhIL-26 to EAE mice immunized with MOG 35–55 .…”

“… 15 Previous studies on IL-26 have shown that results obtained from mouse models using rhIL-26 provide information, which is supportive of human in vitro or in situ studies. 15 , 24 , 25 Before investigating the contribution of IL-26 on BBB permeability in vivo, we first sought to confirm whether rhIL-26 affects mouse BBB ECs in vitro. Mouse brain ECs were isolated and treated with 100 ng/mL rhIL-26, and subsequent expression of TJ molecules JAM-1, ZO-1, and CLDN5 was assessed.…”

Enhanced local production of IL-26 in uncontrolled compared with controlled adult asthma

“…4 It potentiates the chemotactic response of human neutrophils in vitro and enhances endotoxin-induced accumulation of neutrophils and macrophages in the airways in vivo. 4,5 It also displays direct antibacterial properties in experimental models in vitro and in vivo. 6 Moreover, there is evidence for enhanced IL-26 protein in the airways for poorly controlled compared with controlled asthma, among children with the noneosinophilic endotype.…”

“….47 Total lymphocyte count 3 10 60.29 (0.09-0.65) 0.35 (0.12-0.71) .74 Lymphocyte proportion (%) 5 (3-6) 4 (2)(3)(4)(5)(6) .47 Total macrophage count 3 10 66.3 (3.2-9.8) 10.0 (5.5-11.5) .32 Macrophage proportion (%) 90 (87-92) 92 (89-95) .34 Total eosinophil count 3 10 60.05 (0.00-0.18) 0.00 (0.00-0.11) .24 Eosinophil proportion (%) 1 (0-2) 0 (0-1) .16 Total neutrophil count 3 10 60.12 (0.04-0.26) 0.26 (0.16-0.41) .055 Neutrophil proportion (%)…”

<p>Sputum IL-26 Is Overexpressed in Severe Asthma and Induces Proinflammatory Cytokine Production and Th17 Cell Generation: A Case–Control Study of Women</p>

“…In mice, exposure to endotoxin enhances the production of IL-26, IL-6 and IL-8 in the airways. 40 We observed a positive correlation between IL-26 and sputum neutrophils, suggesting an enhanced recruitment of these cells in severe asthma with a possible role of microbial agents. Virus are reported as a major factor of asthma exacerbation, inducing non-specific innate immunity activation involving Th17 cytokines.…”