Anti‐Inflammatory Activities of Melatonin Derivatives in Lipopolysaccharide‐Stimulated <scp>RAW</scp> 264.7 Cells and Antinociceptive Effects in Mice

Phiphatwatcharaded, Chawapon; Topark-Ngarm, Acharawan; Puthongking, Ploenthip; Mahakunakorn, Pramote

doi:10.1002/ddr.21177

Cited by 23 publications

(13 citation statements)

References 28 publications

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“…Subsequently, a range of melatonin doses was selected, and the effect of such doses was investigated through the behavior of cells grown in proliferation medium in order to determine whether growth inhibition resulted from the cytotoxic effect of melatonin on osteoclast precursors or from its inhibitory effect on osteoclast differentiation. It was found that melatonin did not produce cytotoxic effects on the cells in the range of 100-1000 μM, and that coincides with results in the literature (Phiphatwatcharaded et al, 2014).…”

Section: Figuresupporting

confidence: 91%

The inhibitory effect of melatonin on osteoclastogenesis of RAW 264.7 cells in low concentrations of RANKL and MCSF

Jarrar¹,

Altındal²,

Gümüşderelı́oğlu³

2020

Turk J Biol

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RAW 264.7 cells are one of the most recommended cell lines for investigating the activity and differentiation of osteoclasts. These cells differentiate into osteoclasts in the presence of two critical components: receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony stimulating factor (MCSF). Melatonin (MEL) hormone has recently become one of the small molecules used in the field of bone regeneration and bone disease treatment, as it has the ability to inhibit the differentiation of osteoclasts directly by suppression of the NF-κB signaling pathway. The main aim of the current study is to determine sufficient RANKL/MCSF concentrations for differentiation of the cells to osteoclasts and to describe the repressive effect of MEL on the osteoclastogenesis of these cells. In this regard, it was found that 10 ng/mL of RANKL- and MCSF-containing medium is suitable for inducing osteoclastogenesis of the cells. In addition, melatonin at doses in the range of 100–1000 μM does not have a cytotoxic effect. Subsequently, results of tartrate resistant acid phosphatase (TRAP) activity, TRAP staining, and relative expressions of cathepsin K, nuclear factor of activated T cells one (NFATC1), and TRAP genes showed a suppressive effect of MEL —especially 800 μM— on RANKL-induced osteoclastogenesis of these cells.

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Section: Figuresupporting

confidence: 91%

The inhibitory effect of melatonin on osteoclastogenesis of RAW 264.7 cells in low concentrations of RANKL and MCSF

Jarrar¹,

Altındal²,

Gümüşderelı́oğlu³

2020

Turk J Biol

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“…These findings are in accordance with literature as many experiments were performed to study the effect of BMP-2 on osteoclast formation using doses of 100 or 300 ng/mL and no cytotoxic effect was detected when they were used [9,28]. In similar manner, the cytotoxic effect of MEL on RAW 264.7 cells was investigated in the range of 250-2000 µM and MTT results showed no decrease in cell viability [33]. [34].…”

Section: Cell Viabilitysupporting

confidence: 90%

Effect of melatonin/BMP-2 co-delivery scaffolds on the osteoclast activity

Jarrar

Altındal

Gümüşderelı́oğlu

2021

J Mater Sci: Mater Med

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Bone morphogenetic protein two (BMP-2) has been widely used as an osteoinductive agent in the treatment of bone diseases. However, some side effects, such as osteoclast activation have emerged when it was used at high doses. In this study, by considering the osteoclast-suppressing capability of melatonin (MEL), its effect on osteoclast differentiation induced by BMP-2 was investigated. These two factors, MEL and BMP-2, were embedded into chitosan/hydroxyapatite (HAp) scaffolds that were characterized morphologically by scanning electron microscopy (SEM) and micro-computed tomography (μ-CT). Release profiles of MEL and BMP-2 from scaffolds were determined in vitro and then, the differentiation of RAW 264.7 cells to osteoclasts was investigated on the scaffolds. Results of tartrate-resistant acid phosphatase (TRAP) staining, SEM imaging and expression of cathepsin K gene showed that, in the presence of BMP-2, osteoclast differentiation increased, whereas it decreased in MEL and MEL/BMP-2 embedded scaffolds suggesting that melatonin successfully attenuated osteoclast differentiation induced by BMP-2. Thus, the MEL/BMP-2 loaded chitosan/HAp scaffolds that have dual function in enhancing bone formation and inhibiting osteoclast activity are recommended biomaterials in the field of bone regeneration.

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“…In an innate immune response, melatonin can modulate the main cellular components, such as macrophages, NK cells and monocytes, by increasing cellularity or promoting cell activity 30. It has been reported that melatonin has anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages 31. However, no information exists on whether melatonin can alter tumor cells to attenuate an immunosuppressive state.…”

Section: Discussionmentioning

confidence: 99%

Exosomes from Melatonin Treated Hepatocellularcarcinoma Cells Alter the Immunosupression Status through STAT3 Pathway in Macrophages

Liu¹,

Liu²,

Liu³

et al. 2017

Int. J. Biol. Sci.

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Immunosuppression is a significant factor in the progression of tumor invasion and metastasis. Melatonin, a well-known hormone, has certain cytotoxic and immune regulatory effects to inhibit tumor function. Exosomes are small membrane vesicles released by many kinds of cells, which contain different macromolecules, such as mRNAs and microRNAs (miRNAs), and proteins that can mediate communications between cells. Tumor-derived exosomes may cause immunosuppression, however, it is unknown whether melatonin can attenuate an immunosuppressive status by altering the function of tumor-derived exosomes. In the present study, we evaluated the effects of hepatocellularcarcinoma-derived exosomes (Exo-con) and exosomes derived from hepatocellularcarcinoma cells treated with 0.1 mM melatonin (Exo-MT), on the expression of inflammatory factors and programmed death ligand 1(PD-L1) by co-culturing Exo-con and Exo-MT, respectively, with macrophages differentiated from THP-1 cells or RAW264.7 cells. Our in vitro results indicate that Exo-MT can downregulate the expression of PD-L1 on macrophages while Exo-con can upregulate the expression of PD-L1 through flow cytometry and immunofluorescence analysis. In addition, Exo-con upregulates the secretion of cytokines, such as IL-6, IL-10, IL-1β, and TNF-α in macrophages. Accordingly, Exo-MT could attenuate the high expression of these inflammatory cytokines. Furthermore, in vivo experiments confirmed the results found in vitro. PD-L1 expression and cytokine secretion were lower in the Exo-MT group compared with those in the Exo-con group. Working to identify a specific mechanism, our research shows that Exo-MT decreases STAT3 activation compared to the Exo-con group. In summary, we found exosomes from melatonin treated hepatocellularcarcinoma cells alters the immunosupression status through STAT3 pathway in macrophages. Our study may provide a new avenue to investigate the mechanisms of melatonin in regulating an immunosuppressive status.

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Anti‐Inflammatory Activities of Melatonin Derivatives in Lipopolysaccharide‐Stimulated RAW 264.7 Cells and Antinociceptive Effects in Mice

Cited by 23 publications

References 28 publications

The inhibitory effect of melatonin on osteoclastogenesis of RAW 264.7 cells in low concentrations of RANKL and MCSF

The inhibitory effect of melatonin on osteoclastogenesis of RAW 264.7 cells in low concentrations of RANKL and MCSF

Effect of melatonin/BMP-2 co-delivery scaffolds on the osteoclast activity

Exosomes from Melatonin Treated Hepatocellularcarcinoma Cells Alter the Immunosupression Status through STAT3 Pathway in Macrophages

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