Inhibition of MMP-2-Mediated Mast Cell Invasion by NF-κB Inhibitor DHMEQ in Mast Cells

Noma, Naruto; Asagiri, Masataka; Takeiri, Masatoshi; Ohmae, Saori; Takemoto, Kenji; Iwaisako, Keiko; Minato, Nagahiro; Maeda‐Yamamoto, Mari; Simizu, Siro; Umezawa, Kazuo

doi:10.1159/000371419

Cited by 16 publications

(7 citation statements)

References 22 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this ailment, CCL5 is responsible for the recruitment of leukocytes at the site of inflammation [ 56 ]. MMP-2 is a matrix metalloproteinase produced under inflammatory conditions and is involved in the infiltration of inflammation cells, in particular mast cells [ 57 ].…”

Section: Resultsmentioning

confidence: 99%

A Cornflower Extract Containing N-Feruloylserotonin Reduces Inflammation in Human Skin by Neutralizing CCL17 and CCL22 and Inhibiting COX-2 and 5-LOX

Carola

Salazar

Rakers

et al. 2021

Mediators of Inflammation

View full text Add to dashboard Cite

Thymus and Activation-Regulated Chemokine (TARC/CCL17) and Macrophage-Derived Chemokine (MDC/CCL22) are two key chemokines exerting their biological effect via binding and activating a common receptor CCR4, expressed at the surface of type 2 helper T (Th2) cells. By recruiting Th2 cells in the dermis, CCL17 and CCL22 promote the development of inflammation in atopic skin. The aim of this research was to develop a plant extract whose biological properties, when applied topically, could be beneficial for people with atopic-prone skin. The strategy which was followed consisted in identifying ligands able to neutralize the biological activity of CCL17 and CCL22. Thus, an in silico molecular modeling and a generic screening assay were developed to screen natural molecules binding and blocking these two chemokines. N-Feruloylserotonin was identified as a neutraligand of CCL22 in these experiments. A cornflower extract containing N-feruloylserotonin was selected for further in vitro tests: the gene expression modulation of inflammation biomarkers induced by CCL17 or CCL22 in the presence or absence of this extract was assessed in the HaCaT keratinocyte cell line. Additionally, the same cornflower extract in another vehicle was evaluated in parallel with N-feruloylserotonin for cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymatic cellular inhibition. The cornflower extract was shown to neutralize the two chemokines in vitro, inhibited COX-2 and 5-LOX, and demonstrated anti-inflammatory activities due mainly to the presence of N-feruloylserotonin. Although these findings would need to be confirmed in an in vivo study, the in vitro studies lay the foundation to explain the benefits of the cornflower extract when applied topically to individuals with atopic-prone skin.

show abstract

Section: Resultsmentioning

confidence: 99%

A Cornflower Extract Containing N-Feruloylserotonin Reduces Inflammation in Human Skin by Neutralizing CCL17 and CCL22 and Inhibiting COX-2 and 5-LOX

Carola

Salazar

Rakers

et al. 2021

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…The transcriptions of MMP-2/-9 genes are regulated by upstream regulatory factors including NF-κB p65 and c-Jun (56,57). Constitutively active PI3K and NF-κB signaling pathways (58) and blocking PI3K/AKT and NF-κB signaling pathways led to decrease breast cancer cell migration (59). We have found the inhibition of MM-2/-9 activities (Fig.…”

mentioning

confidence: 79%

4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways

Lin

Hsu

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR. K87 decreased the percentage of viable cells in dosedependent manner. K87 suppressed cell mobility, migration and invasion of SCC-4 cells dose-dependently. K87 inhibited the enzymatic activities of MMP-2/9 of SCC-4 cells. Western blot analysis revealed that K87 decreased the protein levels in NF-κBp65, COX-2, ROCK1 and Rho A, PCR indicated that K87 inhibited the gene expression of MMP-2/-7, FAK and ROCK1 mRNA. Furthermore, confocal laser microscopy was used to confirm that K87 inhibited the translocation of RHOA and ROCK1 in SCC-4 cells. EMSA assay also show that K87 suppressed the nuclear activation of NF-κB and these effects are time-dependent. Western blotting assay indicated that expression of NF-κBp105, NF-κBp50 and NF-κBp65 proteins were decreased and these effects are timedependent. Based on these observations, we suggest that K87 may be used as a potential agent for anticancer metastasis of human oral cancer in the future.

show abstract

“…Stimulation with antigen and IgE is known to activate NF-κB in mast cells. We have studied the role of NF-κB on cellular migration in mast cell-like rat RBL-2H3 and mouse primary culture mast cells [ 28 ]. (−)-DHMEQ inhibited antigen/IgE-induced NF-κB activation and expression of its target genes, such as IL-6 and TNF-α.…”

Section: Anti-inflammatory Activity Of Dhmeqmentioning

confidence: 99%

Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ

Ma¹,

Zhang

Sugai

et al. 2021

Cells

Self Cite

View full text Add to dashboard Cite

General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases.

show abstract

Inhibition of MMP-2-Mediated Mast Cell Invasion by NF-κB Inhibitor DHMEQ in Mast Cells

Cited by 16 publications

References 22 publications

A Cornflower Extract Containing N-Feruloylserotonin Reduces Inflammation in Human Skin by Neutralizing CCL17 and CCL22 and Inhibiting COX-2 and 5-LOX

A Cornflower Extract Containing N-Feruloylserotonin Reduces Inflammation in Human Skin by Neutralizing CCL17 and CCL22 and Inhibiting COX-2 and 5-LOX

4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways

Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ

Contact Info

Product

Resources

About