PMC:7544934 / 12938-16177 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7544934","sourcedb":"PMC","sourceid":"7544934","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7544934","text":"LDN treatment diminishes LPS induced cytokine storm\nCytokine storm is a very commonly observed factor in most severe COVID-19 patients and also one of the leading causes of mortality (Coperchini et al., 2020; Rahmati and Moosavi, 2020; Zhang et al., 2020). Peripheral blood of severe COVID-19 patients has also shown a high level of cytokine storm (Wu and Yang, 2020). Keeping in mind the ability of lipopolysaccharide (LPS) to cause sepsis and triggers an uncontrolled systemic inflammatory response in murine macrophage cells (Ramos-Benitez et al., 2018), we treated macrophage cells with LPS (1 µg/ml) in the presence and absence of LDN (5 µM). The dose of LDN chosen is non-toxic (Figure S2) as found in cell viability using MTT (4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay following the standard protocol (Dogra et al., 2019).\nResults demonstrated that LPS treatment significantly induced expression on pro-inflammatory cytokines (IL-1β, IL-6 and mcp-1) whereas, LDN significantly inhibited LPS expression of IL-1β, IL-6 and mcp-1 in macrophage cells (Figure 1(A)). Next, we tested the possible involvement of LPS in inducing the release of pro-inflammatory cytokines, and we also determine the effects of LDN on release of pro-inflammatory mediators in LPS induced macrophage cells (Figure 1(B)). Conditioned media from LPS challenged macrophage cells showed a significantly enhanced release pro-inflammatory mediators (IL-1β, MCP-1 and IL-6) and interestingly we found that LDN treatment attenuated LPS induced IL-1β, MCP1 and IL-6 level (Figure 1(B)). These data suggest that LPS induced macrophage cells, to release - pro-inflammatory mediators, and LDN treatment can significantly abrogate LPS induced release of pro-inflammatory mediators in media. Adipose tissue macrophages (ATMs) is closely linked to this inflammatory condition which leads to numbers of diseases and the ability of High Fat Diet (HFD) feeding on increased LPS uptake and trafficking to macrophages and other targets are well known (Hersoug et al., 2016). Hence in this study, we investigated the effect of HFD on proinflammatory markers expression in purified ATMs. Expression of pro-inflammatory markers such as IL-1β, MCP-1 and IL-6 was induced (Figure 1(C)) whereas LDN attenuates HFD induced pro-inflammatory cytokines expression. Altogether, this data clearly shows that LDN treatment may protect (by reducing elevated M1 cytokines) against inflammation.\nFigure 1. (A) LDN prevents LPS induced pro-inflammatory cytokines expression and release Quantitative mRNA expression of indicated genes (mcp-1, il-6 and Il1b) in murine macrophage cells. (B) ELISA of pro-inflammatory proteins (MCP-1, IL-6 and IL-1β) in conditioned media from LPS challenged murine macrophage cells in the present and absence of LDN (C) Quantitative mRNA expression of IL-1β, mcp-1 and IL-6 in purified ATMs from all group mice. Values are expressed as mean ± SEM (n = 3) from three independent sets of repeats (mean ± SEM ***p \u003c 0.001, **p, ^^p \u003c 0.01 *p,^p \u003c 0.05.) (D) LDN acts as EKR1 inhibitor and improved insulin sensitivity in LPS treated macrophage cells. ERK1/2 (Immunoblot) in RAW cells treated with LPS (1ug/ml) in the presence and absence of 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