Exogenous Gas6 attenuates silica-induced inflammation on differentiated THP-1 macrophages

Shen, Yan; Cui, Xiuqing; Rong, Yi; Xiao, Lili; Zhou, Ting; Chen, Weihong

doi:10.1016/j.etap.2016.05.029

Cited by 15 publications

(13 citation statements)

References 35 publications

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“…In this study, we observed that rGas6 treatment can lead to neurobehavioral improvement, as well as amelioration of brain infarction after MCAO in short and long-term experiments; these findings are consistent with other experimental inflammatory models (Giangola et al, 2013; Llacuna et al, 2010). The study by Yan Shen et al demonstrated an inhibitory effect by Gas6 on acute inflammatory cytokine secretion by macrophages (Shen et al, 2016). Another study, in a sepsis model, confirmed that Gas6 is an anti-inflammatory agent and can prevent organ dysfunction (Giangola et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats

McBride

Zhang

2018

Neurobiology of Disease

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Section: Discussionmentioning

confidence: 99%

Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats

McBride

Zhang

2018

Neurobiology of Disease

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“…Crystalline silica (DQ12, particle diameter <1 μm) was kindly provided by the Institute for Occupational Safety and Health of German Social Accident Insurance (IFA, Germany). The crystalline silica was prepared as previously described . Briefly, the silica particles were weighed and autoclaved at 121 °C for 30 min to eliminate endotoxins and then dried at 55 °C for at least 12 h. Before each experiment, the silica particles were suspended in 1640 medium and sonicated for 15 min (220 V, 50 Hz) to shatter aggregations.…”

Section: Methodsmentioning

confidence: 99%

Triiodothyronine Attenuates Silica-Induced Oxidative Stress, Inflammation, and Apoptosis via Thyroid Hormone Receptor α in Differentiated THP-1 Macrophages

Gan

Yang

Fan

et al. 2020

Chem. Res. Toxicol.

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Alveolar macrophage (AM) injury and inflammatory response are key processes in pathological damage caused by silica. However, the role of triiodothyronine (T3) in silica-induced AM oxidative stress, inflammation, and mitochondrial apoptosis remained unknown. To investigate the possible effects and underlying mechanism of T3 in silica-induced macrophage damage, differentiated human acute monocytic leukemia cells (THP-1) were exposed to different silica concentrations (0, 50, 100, 200, and 400 μg/mL) for 24 h. Additionally, silica-activated THP-1 macrophages were treated with gradient-dose T3 (0, 5, 10, 20, and 40 nM) for 24 h. To illuminate the potential mechanism, we used short hairpin RNA to knock down the thyroid hormone receptor α (TRα) in the differentiated THP-1 macrophages. The results showed that T3 decreased lactate dehydrogenase and reactive oxygen species levels, while increasing cell viability and superoxide dismutase in silica-induced THP-1 macrophages. In addition, silica increased the expression of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), and T3 treatment reduced those pro-inflammatory cytokines secretion. Compared with silica-alone treated groups, cells treated with silica and T3 restored the mitochondrial membrane potential loss and had reduced levels of cytochrome c and cleaved caspase-3 expressions. Lastly, we observed that TRα-knockdown inhibited the protective effects of T3 silica-induced THP-1 macrophages. Together, these findings revealed that T3 could serve as a potential therapeutic target for protection against silica-induced oxidative stress, inflammatory response, and mitochondrial apoptosis, which are mediated by the activation of the T3/TRα signal pathway.

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“…In an independent study, MerTK activation was shown to inhibit TNF-α production by LPS-stimulated mouse macrophages [65]. Additionally, exogenous Gas6 treatment on phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages decreases TNF-α, IL-1β and IL-6 mRNA and protein levels, providing further evidence that TAM receptor signaling blocks M1 polarization [66]. It has been shown that Protein S activation of either MerTK or Tyro3 inhibits LPS and IFN-γ induced M1 polarization of peritoneal and tumor-derived mouse macrophages, indicated by decreased expression of M1 marker genes Il1 , Il6 , Cd86 and Tnf [67].…”

Section: Main Textmentioning

confidence: 99%

Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment

Myers¹,

Amend²,

2019

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Tumor-associated macrophages are an abundant cell type in the tumor microenvironment. These macrophages serve as a promising target for treatment of cancer due to their roles in promoting cancer progression and simultaneous immunosuppression. The TAM receptors (Tyro3, Axl and MerTK) are promising therapeutic targets on tumor-associated macrophages. The TAM receptors are a family of receptor tyrosine kinases with shared ligands Gas6 and Protein S that skew macrophage polarization towards a pro-tumor M2-like phenotype. In macrophages, the TAM receptors also promote apoptotic cell clearance, a tumor-promoting process called efferocytosis. The TAM receptors bind the “eat-me” signal phosphatidylserine on apoptotic cell membranes using Gas6 and Protein S as bridging ligands. Post-efferocytosis, macrophages are further polarized to a pro-tumor M2-like phenotype and secrete increased levels of immunosuppressive cytokines. Since M2 polarization and efferocytosis are tumor-promoting processes, the TAM receptors on macrophages serve as exciting targets for cancer therapy. Current TAM receptor-directed therapies in preclinical development and clinical trials may have anti-cancer effects though impacting macrophage phenotype and function in addition to the cancer cells.

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Exogenous Gas6 attenuates silica-induced inflammation on differentiated THP-1 macrophages

Cited by 15 publications

References 35 publications

Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats

Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats

Triiodothyronine Attenuates Silica-Induced Oxidative Stress, Inflammation, and Apoptosis via Thyroid Hormone Receptor α in Differentiated THP-1 Macrophages

Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment

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