• Journal of Plant Biotechnology
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• 제42권4호
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• pp.277-283
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• 2015

Plant genome analyses, including Arabidopsis thaliana showed a large gene family of plant receptor kinases with various extracellular ligand-binding domain. Now intensively studies to understand physiological and cellular functions for higher plant receptor kinases in diverse and complex biological processes including plant growth, development, ligands perception including steroid hormone and plant-microbe interactions. Brassinosteroids (BRs) as a one of well know steroid hormone are plant growth hormones that control biomass accumulation and also tolerance to many biotic and abiotic stress conditions and hence are of relevance to agriculture. BRI1 receptor kinase, which is localized in plasma membrane in the cell sense BRs and it bind to a receptor protein known as BRASSINOSTEROID INSENSITIVE 1 (BRI1). Recently, we reported that BRI1 and its co-receptor, BRI1-ASSOCIATED KINASE (BAK1) autophosphorylated on tyrosine residue (s) in vitro and in vivo and thus are dual-specificity kinases. Other plant receptor kinases are also phosphorylated on tyrosine residue (s). Post-translational modifications (PTMs) can be studied by altering the residue modified by directed mutagenesis to mimic the modified state or to prevent the modification. These approaches are useful to not only characterize the regulatory role of a given modification, but may also provide opportunities for plant improvement.

• BMB Reports
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• 제35권4호
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• pp.371-376
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• 2002

The receptor activator of nuclear factor kappa B (RANK) is a member of the tumor necrosis factor (TNF) receptor superfamily. It plays a critical role in osteoclast differentiaion, lymph node organogenesis, and mammary gland development. The stimulation of RANK causes the activation of transcription factors NF-${\kappa}B$ and activator protein 1 (AP1), and the mitogen activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). In the signal transduction of RANK, the recruitment of the adaptor molecules, TNF receptor-associated factors (TRAFs), is and initial cytoplasmic event. Recently, the association of the MAPK kinase kinase, transforming growth factor-$\beta$-activated kinase 1 (TAK1), with TRAF6 was shown to mediate the IL-1 signaling to NF-${\kappa}B$ and JNK. We investigated whether or not TAK1 plays a role in RANK signaling. A dominant-negative form of TAK1 was discovered to abolish the RANK-induced activation of AP1 and JNK. The AP1 activation by TRAF2, TRAF5, and TRAF6 was also greatly suppressed by the dominant-negative TAK1. the inhibitory effect of the TAK1 mutant on RANK-and TRAF-induced NF-${\kappa}B$ activation was also observed, but less efficiently. Our findings indicate that TAK1 is involved in the MAPK cascade and NF-${\kappa}B$ pathway that is activated by RANK.

• Annals of Clinical Neurophysiology
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• 제19권1호
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• pp.74-76
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• 2017

Muscle specific tyrosine kinase (MuSK) myasthenia gravis (MG) is a rare subtype of MG, which is immunologically distinct and differential therapeutic response. Though MG is often associated with other autoimmune disorders or malignancy, concurrence of other disease and MuSK MG has been infrequently reported. We present a patient of MuSK MG associated with multicentric Castelman disease.

• BMB Reports
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• 제51권6호
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• pp.308-313
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• 2018

Small-molecule inhibitors are widely used to treat a variety of inflammatory diseases. In this study, we found a novel anti-inflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), the inhibitor of ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$), and their upstream kinases, $I{\kappa}B$ kinase (IKK) ${\alpha}/{\beta}$, mitogen-activated protein kinase kinase (MKK) 3/6, and MKK4. Furthermore, the expression of IL-1 receptor-associated kinase 1 (IRAK1) that regulates $NF-{\kappa}B$, p38, and the JNK signaling pathways, was also increased by MPQP. These results indicate that MPQP regulates the IRAK1-mediated inflammatory signaling pathways by targeting IRAK1 or its upstream factors.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권5호
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• pp.287-293
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• 2009

Cell survival is the result of a balance between programmed cell death and cellular proliferation. Cell membrane receptors and their associated signal transducing proteins control these processes. Of the numerous receptors and signaling proteins, epidermal growth factor receptor (EGFR) is one of the most important receptors involved in signaling pathways implicated in the proliferation and survival of cancer cells. EGFR is often highly expressed in human tumors including oral squamous cell carcinomas, and there is increasing evidence that high expression of EGFR is correlated with poor clinical outcome of common human cancers. Therefore, we examined the antiproliferative activity of gefitinib, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), in head and neck cancer cell lines. SCC-9, KB cells were cultured and growth inhibition activity of gefitinib was measured with MTT assay. To study influence of gefitinib in cell cycle, we performed cell cycle analysis with flow cytometry. Western blot was done to elucidate the expression of EGFR in cell lines and phosphorylation of EGFR and downstream kinase protein, Erk and Akt. Significant growth inhibition was observed in SCC-9 cells in contrast with KB cells. Also, flow cytometric analysis showed G1 phase arrest only in SCC-9 cells. In Western blot analysis for investigation of EGFR expression and downstream molecule phosphorylation, gefitinib suppressed phosphorylation of EGFR and downstream protein kinase Erk, Akt in SCC-9. However, in EGFR positive KB cells, weak expression of active form of Erk and Akt and no inhibitory activity of phosphorylation in Erk and Akt was observed. The antiproliferative activity of gefitinib was not correlated with EGFR expression and some possibility of phosphorylation of Erk and Akt as a predictive factor of gefitinib response was emerged. Further investigations on more reliable predictive factor indicating gefitinib response are awaited to be useful gefitinib treatment in head and neck cancer patients.

• International Journal of Oral Biology
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• 제47권1호
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• pp.1-8
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• 2022

Inflammation is a protective mechanism against pathogens, but if maintained continuously, it destroys tissue structures. Aggregatibacter actinomycetemcomitans is a gram-negative, facultative anaerobic bacterium often found in severe periodontitis. A. actinomycetemcomitans invades epithelial cells and triggers inflammatory response in the immune cells. In this study, we investigated the effect of water-soluble rosehip extract on A. actinomycetemcomitans-induced inflammatory responses. A human monocytic cell line (THP-1) was differentiated to macrophages by phorbol 12-mystristate 13-acetate treatment. The cytotoxic effect of extract was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of extract on bacterial growth were examined by measuring the optical densities using a spectrophotometer. THP-1-derived macrophages were infected A. actinomycetemcomitans after extract treatment, and culture supernatants were analyzed for cytokine production using enzyme-linked immunosorbent assay. Protein expression was measured by western blotting. Extract was not toxic to THP-1-derived macrophages. A. actinomycetemcomitans growth was inhibited by 1% extract. The extract suppressed A. actinomycetemcomitans-induced tumor necrosis factor-α, interleukin (IL)-1β, and IL-8 production. It also decreased mitogen-activated protein kinase (MAP kinase) and nuclear factor-κB (NF-κB) phosphorylation. Moreover, the extract inhibited the expression of inflammasome components, including nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3, Absent in Melanoma 2, and apoptosis associated speck-like protein containing a CARD. And cysteine-aspartic proteases-1 and IL-1β expression were decreased by the extract. In summary, extract suppressed A. actinomycetemcomitans growth and decreased inflammatory cytokine production by inhibiting activation of MAP kinase, NF-κB, and inflammasome signaling. Rosehip extract could be effective in the treatment of periodontal inflammation induced by A. actinomycetemcomitans infection.

• 한국균학회지
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• 제46권2호
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• pp.161-176
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• 2018

진균류 유래의 ${\beta}$-glucan은 pathogen-associated molecular patterns의 일종이기도 하며 면역촉진과 항암작용을 나타냄이 알려져 있지만 세포 내 신호전달에 관해서는 알려진 바가 많지 않다. 대식세포주인 RAW264.7 세포에 불로초에서 추출한 ${\beta}$-glucan을 처리하였을 때 세포막에서는 덱틴-1, toll-like receptor 2, 4, 6의 발현이 증가되었으며, 세포 내에서는 macrophage inflammatory protein (MIP)-1a, MIP-$1{\beta}$, MIP-$1{\gamma}$, IL-$1{\beta}$ 그리고 tumor necrosis factor (TNF)-${\alpha}$의 발현이 증가되었다. 또한 대식세포주에 불로초의 ${\beta}$-glucan과 PI3K 또는 MEK1/MEK2 억제제를 각각 처리하였을 때에 세포 내의 MIP-1a, MIP-$1{\beta}$, MIP-$1{\gamma}$, interleukin-$1{\beta}$, TNF-${\alpha}$의 발현이 감소되었다. 따라서 불로초의 ${\beta}$-glucan은 대식세포에서 MyD88의 경로인 PI3K/Akt를 경유할 뿐만 아니라 MEK 경로를 활성화시킴으로써 다양한 면역조절작용이 가능한 것으로 여겨진다.

• Journal of Microbiology and Biotechnology
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• 제18권6호
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• pp.1170-1178
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• 2008

The cyclopentenone prostaglandins (cyPGs) prostaglandin $A_1$ ($PGA_1$) and 15-deoxy-${\Delta}^{12,14}$-prostaglandin $J_2$ (15d-$PGJ_2$) have been reported to exhibit antiinflammatory activity in activated monocytes/macrophages. However, the effects of these two cyPGs on the expression of cytokine genes may differ. In this study, we investigated the mechanism of action of $PGA_1$ in lipopolysaccharide (LPS)-induced expression of inter leu kin (IL)-10 mRNA in mouse peritoneal macrophages. 15d-$PGJ_2$ inhibited expression of LPS-induced IL-10, whereas $PGA_1$ increased LPS-induced IL-10 expression. This synergistic effect of $PGA_1$ on LPS-induced IL-10 expression reached a maximum as early as 2 h after simultaneous $PGA_1$ and LPS treatment ($PGA_1$/LPS), and did not require new protein synthesis. The synergistic effect of $PGA_1$ was inhibited by GW9662, a specific peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$ antagonist, and Bay-11-7082, a NF-${\kappa}B$ inhibitor. The extracellular signal-regulated kinases (ERK) inhibitor PD98059 increased the expression of $PGA_1$/LPS-induced IL-10 mRNA, rather than inhibiting the IL-10 expression. Moreover, $PGA_1$ inhibited LPS-induced ERK phosphorylation. The synergistic effect of $PGA_1$ on LPS-induced IL-10 mRNA and protein production was inhibited by p38 inhibitor PD169316, and $PGA_1$ increased LPS-induced p38 phosphorylation. In the case of stress-activated protein kinase/c-Jun $NH_2$-terminal kinase (SAPK/JNK), the SAPK/JNK inhibitor SP600125 did not inhibit IL-10 mRNA synthesis but inhibited the production of IL-10 protein remarkably. These results suggest that the synergistic effect of $PGA_1$ on LPS-induced IL-10 expression is NF-${\kappa}B$-dependent and mediated by mitogen-activated protein (MAP) kinases, p38, and SAPK/JNK signaling pathways, and also associated with the $PPAR{\gamma}$ pathway. Our data may provide more insight into the diverse mechanisms of $PGA_1$ effects on the expression of cytokine genes.

• 한국식생활문화학회지
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• 제33권4호
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• pp.337-344
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• 2018

Germinated brown rice (GBR, Orysa sartiva L.) has been reported to have anti-obesity and anti-inflammatory effects. However, the mechanisms underlying these effects in adipocytes are not fully understood. Therefore, this study was conducted to explore the anti-inflammatory mechanisms of GBR on lipopolysaccharide (LPS)-stimulated 3T3-L1 adipocytes. 3T3-L1 adipocytes were pretreated with GBR extracts (0-20 mg/mL) 1 h before LPS stimulation. The mRNA expression of adipokines and Toll-like receptor 4 (TLR4) were measured by RT-PCR. The protein expressions of TLR4-related molecules were detected by western blotting and nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) activation was measured. Our results showed that GBR extract dose-dependently inhibited mRNA expression of LPS-induced tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). GBR extract was found to inhibit LPS-induced mRNA expression of TLR4 and protein expression of both myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factor 6 (TRAF6). Furthermore, GBR extract significantly inhibited extracellular receptor-activated kinase (ERK) phosphorylation and $NF-{\kappa}B$ activation. These results suggest that GBR extract has the anti-inflammatory effects on LPS-induced inflammation via inhibition of TLR4 signaling, includingthe ERK and $NF-{\kappa}B$ signaling pathways, in adipocytes.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.395-402
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• 2020

This study has investigated the effect of a potent bioflavonoid, troxerutin, on diabetes-induced changes in pro-inflammatory mediators and expression of microRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissue of type-I diabetic rats. Male Wistar rats were randomly divided into four groups (n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10 weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment. Inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II (COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samples by enzyme-linked immunosorbent assay. Gene expressions for transcription factor NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associated factor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerase chain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1, TRAF-6, NF-κB, and protein levels of cytokines IL-1β, IL-6, TNF-α, adhesion molecules ICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a as compared with healthy rats (p < 0.05 to p < 0.01). However, one month treatment of diabetic rats with troxerutin restored glucose and insulin levels, significantly decreased expression of inflammatory genes and pro-inflammatory mediators and increased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). In healthy rats, troxerutin had significant reducing effect only on NF-κB, TNF-α and COX-II levels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin prevented the activation of NF-κB-dependent inflammatory signaling in the aorta of diabetic rats, and this response may be regulated by microRNA-146a.