All-trans retinoic acid increases NF-κB activity in PMA-stimulated THP-1 cells upon unmethylated CpG challenge by enhancing cell surface TLR9 expression

Trinh, Tam Anh; Hoang, Thi Xoan; Kim, Jae Young

doi:10.1007/s11010-020-03817-4

Cited by 6 publications

(4 citation statements)

References 54 publications

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“…As shown in Figure A–G, WYJ-2 had no agonistic activity from 0.01 to 50 μM compared with the blank group. Most human TLR members can be expressed in differentiated THP-1 macrophages. − Therefore, we knocked down the TLR2 gene in THP-1-differentiated macrophages using siRNA and detected downstream cytokine interleukin-6 (IL-6) levels to evaluate whether WYJ-2 activates other human TLRs. As shown in Figure H, there was no significant difference in IL-6 levels between the vehicle and WYJ-2-treated groups.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of 3-(2H-Chromen-3-yl)-5-aryl-1,2,4-oxadiazole Derivatives as Novel Toll-like Receptor 2/1 Agonists That Inhibit Lung Cancer In Vitro and In Vivo

Wang,

Cheng,

Liu

et al. 2024

J. Med. Chem.

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Toll-like receptor (TLR) 2 is a transmembrane receptor that participates in the innate immune response by forming a heterodimer with TLR1 or TLR6. TLR2 agonists play an important role in tumor therapy. Herein, we synthesized a series of 3-(2Hchromen-3-yl)-5-aryl-1,2,4-oxadiazole derivatives and identified WYJ-2 as a potent small and selective molecule agonist of TLR2/1, with an EC 50 of 18.57 ± 0.98 nM in human TLR2 and TLR1 transient-cotransfected HEK 293T cells. WYJ-2 promoted the formation of TLR2/1 heterodimers and activated the nuclear factor kappa B (NF-κB) signaling pathway. Moreover, our study indicated that WYJ-2 could induce pyroptosis in cancer cells, mediated by activating the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. WYJ-2 exhibited effective anti-non-small cell lung cancer (NSCLC) activity in vitro and in vivo. The discovery that activating TLR2/1 induces pyroptosis in cancer cells may highlight the prospects of TLR2/1 agonists in cancer treatment in the future.

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Section: Resultsmentioning

confidence: 99%

Design and Synthesis of 3-(2H-Chromen-3-yl)-5-aryl-1,2,4-oxadiazole Derivatives as Novel Toll-like Receptor 2/1 Agonists That Inhibit Lung Cancer In Vitro and In Vivo

Wang,

Cheng,

Liu

et al. 2024

J. Med. Chem.

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“…In vitro anti-inflammatory functions have been reported in LPS-stimulated macrophages, in which RA doses from 10 to 100 mM diminish NF-κB activity. Conversely, in macrophages stimulated with different pro-inflammatory stimuli, the addition of lower concentrations ranging from 10 nM to 1 mM has shown the opposite effect, enhancing NF-κB activity, increasing IL-1β production, and inducing a metabolic shift [220,221]. On the other hand, the anti-inflammatory effects of this vitamin have been observed in a sepsis model in mice, decreasing NF-κB target genes expression [222][223][224]; also, during parainfluenza virus infection in guinea pigs, RA treatment has been reported to diminish leukocyte infiltration and promote the expression of muscarinic receptors in the lungs improving their function [225].…”

Section: Functions In the Inflammatory Responsementioning

confidence: 98%

How Micronutrients Fuel Immune System At the Molecular Level: An Approach to the Immune Response Against Respiratory Viruses

Jiménez-Uribe

Ocampo-Hernández

Aranciba-Hernández

et al. 2022

Cell Physiol Biochem

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Viral respiratory infections could range from a common cold to severe pneumonia, and their resolution mainly relies on appropriate immune system function. The widespread popular knowledge that nutritional habits influence immune system function has been demonstrated over the past decades in which increasing scientific evidence unveils certain nutrients as critical drivers of immunity. Micronutrients encompass minerals and vitamins necessary for a broad range of biological processes; since their deficiency could cause several clinical manifestations, such as weakness, growth retardation, and susceptibility to infections; hence, micronutrients represent one of the multiple factors that modulate immune function. Among micronutrients are those that act mainly as antioxidants, regulating gene expression and as a structural part of proteins for their proper function. Here, we review how some of the most recognized micronutrients are participating at the molecular level in each step of the innate and adaptive immune response against viruses focusing on viral respiratory tract infections, such as those caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

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“…The species‐specific expression patterns of TLR9 in mice and humans account for the fundamental functional differences. However, distinct patterns of activation induced by CpG DNA and LPS in human monocytes 60–61 suggest that TLR9 expression is induced and not constitutive, whereas TLR4 is constitutively expressed in human monocytes.…”

Section: Immunogenicity Of Bacterial Dna Containing Cpg Motifsmentioning

confidence: 99%

The role of bacterial DNA containing CpG motifs in diseases

Zhou

Deng

2021

Journal of Leukocyte Biology

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Bacterial DNA containing unmethylated CpG motifs can activate immune cells to release proinflammatory cytokines. Here, the role of bacterial DNA containing CpG motifs in diseases with a focus on arthritis is discussed. Our studies demonstrate that the intraarticular injection of bacterial DNA and oligodeoxynucleotides containing CpG motifs (CpG ODN) induced arthritis. The induction of arthritis involves the role of macrophages over other cells such as neutrophils, NK cells, and lymphocytes. TNF-and TNFRI play an important role in the development of arthritis. NF-B also plays a critical regulatory role in arthritis. Systemic anti-inflammatory treatment, along with antibiotic therapy, has beneficial effects on the course and the outcome of bacterial arthritis. Thus, future treatment strategies for bacterial arthritis should include attempts to minimizing bacterial growth while blocking the proinflammatory effects of the bacterial DNA. Significant therapeutic efficiency has also been shown by CpG ODN-mediated Th1 immune activation in mouse models of cancer, infectious disease, and allergy/asthma.

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All-trans retinoic acid increases NF-κB activity in PMA-stimulated THP-1 cells upon unmethylated CpG challenge by enhancing cell surface TLR9 expression

Cited by 6 publications

References 54 publications

Design and Synthesis of 3-(2H-Chromen-3-yl)-5-aryl-1,2,4-oxadiazole Derivatives as Novel Toll-like Receptor 2/1 Agonists That Inhibit Lung Cancer In Vitro and In Vivo

Design and Synthesis of 3-(2H-Chromen-3-yl)-5-aryl-1,2,4-oxadiazole Derivatives as Novel Toll-like Receptor 2/1 Agonists That Inhibit Lung Cancer In Vitro and In Vivo

How Micronutrients Fuel Immune System At the Molecular Level: An Approach to the Immune Response Against Respiratory Viruses

The role of bacterial DNA containing CpG motifs in diseases

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