Anti-Interleukin-8 monoclonal antibody, clone 8M6

Background: Monocyte-derived macrophages are key regulators and producers of reactive oxygen and nitrogen species (ROS/RNS). Pre-clinical and clinical studies suggest that cold physical plasma may be beneficial in the treatment of inflammatory conditions via the release of ROS/RNS. However, it is unknown how plasma treatment affects monocytes and their differentiation profile. Methods: Naive or phorbol-12-myristate-13-acetate (PMA)-pulsed THP-1 monocytes were exposed to cold physical plasma. The cells were analyzed regarding their metabolic activity as well as flow cytometry (analysis of viability, oxidation, surface marker expression and cytokine secretion) and high content imaging (quantitative analysis of morphology. Results: The plasma treatment affected THP-1 metabolisms, viability, and morphology. Furthermore, a significant modulation CD55, CD69, CD271 surface-expression and increase of inflammatory IL1 beta, IL6, IL8, and MCP1 secretion was observed upon plasma treatment. Distinct phenotypical changes in THP-1 cells arguing for a differentiation profile were validated in primary monocytes from donor blood. As a functional outcome, plasma-treated monocytes decreased the viability of co-cultured melanoma cells to a greater extent than their non-treated counterparts. Conclusions: Our results suggest plasma-derived ROS/RNS shaped a differentiation profile in human monocytes as evidenced by their increased inflammatory profile (surface marker and cytokines) as well as functional outcome (tumor toxicity).

Particulate matter (PM) has been implicated as a risk factor for human airway disorders. However, the biological mechanisms underlying the correlation between PM exposure and adverse airway effects have not yet been fully clarified. The objective of this study was to explore the possible role of early growth response gene 1 (Egr-1) in PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction in vitro and in vivo. Particulate matter exposure induced a rapid Egr-1 expression in human bronchial epithelial (HBE) cells and in mouse lungs. Genetic blockage of Egr-1 markedly reduced PM-induced inflammatory cytokines, e.g., IL6 and IL8, and MUC5AC in HBE cells, and these effects were mechanistically mediated by the nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) pathways, respectively. Egr-1-knockout mice displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Moreover, polycyclic aromatic hydrocarbons (PAHs) contained in the PM also induced Egr-1 expression, and also played a role in the inflammatory responses and mucus production. Taken together, our data reveal novel Egr-1 signaling that mediates the NF-kappa B and AP-1 pathways to orchestrate PM-induced pulmonary inflammation and mucus hyperproduction, suggesting that Egr-1 inhibition could be an effective therapeutic approach for airway disorders or disease exacerbations induced by airborne particulate pollution.