Microarray Analysis of Gene Expression Profiles in Response to Treatment with Melatonin in Lipopolysaccharide Activated RAW 264.7 Cells

Ban, Ju Yeon; Kim, Bum Sik; Kim, Soo Cheol; Kim, Dong Hwan; Chung, Joo‐Ho

doi:10.4196/kjpp.2011.15.1.23

Cited by 28 publications

(18 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Melatonin suppressed LPS-induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein levels in the murine macrophage cell line Raw264.7 [100]. A microarray analysis of gene expression in LPS-activated Raw cells confirmed the melatonin-induced anti-inflammatory profile [101]. Melatonin also downregulated chemokine expression in the BV2 murine microglial cell line following LPS stimulation [102].…”

Section: Pleiotropic Actions Of Melatonin Administration On the Immentioning

confidence: 99%

Melatonin: Buffering the Immune System

Carrillo-Vico

Lardone

Álvarez-Sánchez

et al. 2013

IJMS

586

455

View full text Add to dashboard Cite

Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

show abstract

Section: Pleiotropic Actions Of Melatonin Administration On the Immentioning

confidence: 99%

Melatonin: Buffering the Immune System

Carrillo-Vico

Lardone

Álvarez-Sánchez

et al. 2013

IJMS

586

455

View full text Add to dashboard Cite

show abstract

“…The zymosan-induced TLR2-NF-κB pathway activation results in melatonin production that acts through MT2-melatonin receptors and increases the expression of the membrane protein dectin-1, which is crucial for fungal phagocytosis. Moreover, melatonin in the μM-mM range, which is not toxic for RAW 264.7 cells [107], inhibits TNF, IL-1β, IL-6, IL-8, and IL-10 synthesis and attenuates the up-regulation of COX-2 and iNOS [108]. These effects are due to melatonin-induced inhibition of the expression of myeloid differentiation factor 88 (MyD88), which is one of the first steps in the canonical cascade that links TLR4 to NF-κB activation.…”

Section: The Immune-pineal Axis: the Nf-κb Pathway Coordinates Pinmentioning

confidence: 99%

Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells

Markus

Cecon

Pires-Lapa

2013

IJMS

118

105

View full text Add to dashboard Cite

Pineal gland melatonin is the darkness hormone, while extra-pineal melatonin produced by the gonads, gut, retina, and immune competent cells acts as a paracrine or autocrine mediator. The well-known immunomodulatory effect of melatonin is observed either as an endocrine, a paracrine or an autocrine response. In mammals, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-κB activation in pinealocytes and immune competent cells. Therefore, pathogen- or danger-associated molecular patterns transiently switch the synthesis of melatonin from pinealocytes to immune competent cells, and as the response progresses melatonin inhibition of NF-κB activity leads these cells to a more quiescent state. The opposite effect of NF-κB in pinealocytes and immune competent cells is due to different NF-κB dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-κB is called the immune-pineal axis. Finally, we discuss how this concept might be relevant to a better understanding of pathological conditions with impaired melatonin rhythms and hope it opens new horizons for the research of side effects of melatonin-based therapies.

show abstract

“…Under insulin-and noninsulin-stimulated conditions, PO resulted in upregulation of the following transcripts: miR1970, LPS-regulated genes (Ifit3, Clec4a3, Slc22a3, and C3ar1) (21)(22)(23)(24), G0s2, and Ar16, while Tweak gene expression was downregulated. Opposing regulatory transcripts, i.e., those that were upregulated under insulin-stimulated conditions and downregulated under noninsulin-stimulated conditions, were also found and included, for example, transcripts involved in cell growth (Map3k13 and Slc30af) (25,26) and FFA metabolism and development of NAFLD (fatty acid-binding protein 5 or Fabp5) (27), as well as the predicted pseudogenes Gm3601 and H2-K2 ( Figure 8E).…”

Section: Studies In Humansmentioning

confidence: 99%

Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance

Hernández¹,

Kahl²,

Seelig³

et al. 2017

Journal of Clinical Investigation

159

130

View full text Add to dashboard Cite

H and ex vivo2 H magnetic resonance spectroscopy before and during hyperinsulinemiceuglycemic clamps with isotope dilution. Mice underwent identical clamp procedures and hepatic transcriptome analyses.RESULTS. PO administration decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively. Hepatic triglyceride and ATP content rose by 35% and 16%, respectively. Hepatic gluconeogenesis increased by 70%, and net glycogenolysis declined by 20%. Mouse transcriptomics revealed that PO differentially regulates predicted upstream regulators and pathways, including LPS, members of the TLR and PPAR families, NF-κB, and TNF-related weak inducer of apoptosis (TWEAK). CONCLUSION.Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD. PO results in increased circulating TG, glucagon, and incretins. After PO administration, TG in plasma rose by 59% (area under the time curve [AUC], P < 0.001) and by 156% in chylomicrons (AUC, P = 0.009) (Figure 2A). The AUC for plasma free fatty acids (FFA) ( Figure 2B) and insulin concentrations ( Figure 2C) was unchanged, while the AUC for plasma C-peptide was 28% higher after PO ingestion versus VCL (P < 0.005, Figure 2D). Of note, FFA were increased at 300, 420, and 480 minutes. Blood glucose levels were not different between PO-and VCL-treated groups ( Figure 2E). Plasma glucagon rose by 41% (AUC, P < 0.0001) only after PO ingestion ( Figure 2F). Also, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels were markedly increased and remained elevated after PO ingestion (both P < 0.005) (Supplemental Figure 2; supplemental material available online with this article; https://doi.org/10.1172/ JCI89444DS1). Circulating levels of TNF-α, IL-6, fetuin-A, chemerin, omentin, and cortisol were not different between PO and VCL groups (P > 0.5 for all) (Supplemental Table 1). REGISTRATION. The Journal of Clinical Investigation C L I N I C A L M E D I C I N EPO induces insulin resistance at whole-body, liver, and adipose tissue levels. Insulin sensitivity was measured using hyperinsulinemic-euglycemic clamp tests in healthy humans. Steady state was reached (Supplemental Figure 1), and pertinent parameters were analyzed during this time. PO ingestion reduced WBIS by 25% compared with VCL treatment (P = 0.0005, Figure 3A). Furthermore, after PO, volunteers also showed a decrease of 22% (P = 0.002) in the rate of glucose disappearance (Rd), mostly due to a 33% (P = 0.01) reduction in glucose oxidation (GOX), while the rate of nonoxidative glucose disposal remained unchanged

show abstract

Microarray Analysis of Gene Expression Profiles in Response to Treatment with Melatonin in Lipopolysaccharide Activated RAW 264.7 Cells

Cited by 28 publications

References 24 publications

Melatonin: Buffering the Immune System

Melatonin: Buffering the Immune System

Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells

Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance

Contact Info

Product

Resources

About