• Journal of Microbiology and Biotechnology
• /
• v.27 no.1
• /
• pp.49-56
• /
• 2017

In the human airway, mucus exists to protect the respiratory system as a primary barrier of the innate immune system. However, hyperexpressed mucus limits airflow, resulting in a decrease of lung function. Among more than 20 mucin family members, MUC5AC and MUC5B are major glycoproteins in human airway mucus. The epidermal growth factor receptor (EGFR) signaling pathway is one of the mechanisms of these mucins expression and specificity protein-1 (Sp1) transcription factor is the downstream signal of this pathway, playing pivotal roles in mucin expression. Even though there are some drugs for treating mucus hypersecretion, no drug has proven effects on humans. We found that the flavonoid tilianin regulated MUC5AC expression and also inhibited Sp1 phosphorylation. In this study, we investigated how tilianin would modulate EGFR signaling and regulate mucin production. In conclusion, tilianin inhibited MUC5AC expression mediated via modulating the EGFR-MEK-ERK-Sp1 signaling pathway in NCI-H292 human airway epithelial cells. This study may provide the basis for the novel treatment of mucus hypersecretion.

• The Korean Journal of Mycology
• /
• v.38 no.2
• /
• pp.89-94
• /
• 2010

Plant pathogenic fungi are the most diverse and drastic causal agents of crop diseases threatening stable food production all over the world. Plant have evolved efficient innate immune system to scout and counterattack fungal invasion and pathogenic fungi also developed virulence system to nullify plant resistance machinery or signaling pathways and to propagate and dominate within their niche. A growing body of evidences suggests that post translational modifications (PTMs) and selective/nonselective degradations of proteins involved in virulence expression of plant pathogenic fungi and plant defense machinery should play pivotal roles during the compatible and incompatible interactions. This review elucidates recent investigations about the effects of PTMs and protein degradations on host defense and fungal pathogens' invasions.

• Clinical and Experimental Pediatrics
• /
• v.64 no.4
• /
• pp.141-148
• /
• 2021

There are very scant data on the epidemiology of primary immunodeficiency diseases (PIDs) in Korea. Here we attempted to estimate the PID epidemiology and disease burden in Korea. A systematic review was performed of studies retrieved from the PubMed, KoreaMed, and Google Scholar databases. Studies on PIDs published in Korean or English between January 2001 and November 2018 were analyzed. The number of PID patients and the healthcare costs were estimated from Health Insurance Review and Assessment Service (HIRA) Korea data for 2017. A total of 398 PID patients were identified from 101 reports. Immunodeficiencies affecting cellular and humoral immunity were reported in 11 patients, combined immunodeficiency with associated or syndromic features in 40, predominantly antibody deficiencies in 144, diseases of immune dysregulation in 58, congenital defects of phagocytes in 104, defects in the intrinsic and innate immunity in 1, auto-inflammatory disorders in 4, complement deficiencies in 36, and phenocopies of PID in none. From the HIRA reimbursement data, a total of 1,162 outpatients and 306 inpatients were treated for 8,166 and 6,149 days, respectively. In addition, reimbursement was requested for 8,200 outpatient and 1,090 inpatient cases and $1,924,000 and $4,715,000 were reimbursed in 2017, respectively. This study systematically reviewed published studies on PID and analyzed the national open data system of the HIRA to estimate the disease burden of PID, for the first time in Korea.

• Molecules and Cells
• /
• v.44 no.5
• /
• pp.281-291
• /
• 2021

Tissue-resident macrophages play an important role in maintaining tissue homeostasis and innate immune defense against invading microbial pathogens. Brain-resident macrophages can be classified into microglia in the brain parenchyma and non-parenchymal brain macrophages, also known as central nervous system-associated or border-associated macrophages, in the brain-circulation interface. Microglia and non-parenchymal brain macrophages, including meningeal, perivascular, and choroid plexus macrophages, are mostly produced during embryonic development, and maintained their population by self-renewal. Microglia have gained much attention for their dual roles in the maintenance of brain homeostasis and the induction of neuroinflammation. In particular, diverse phenotypes of microglia have been increasingly identified under pathological conditions. Single-cell phenotypic analysis revealed that microglia are highly heterogenous and plastic, thus it is difficult to define the status of microglia as M1/M2 or resting/activated state due to complex nature of microglia. Meanwhile, physiological function of non-parenchymal brain macrophages remain to be fully demonstrated. In this review, we have summarized the origin and signatures of brain-resident macrophages and discussed the unique features of microglia, particularly, their phenotypic polarization, diversity of subtypes, and inflammasome responses related to neurodegenerative diseases.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.23 no.5
• /
• pp.986-992
• /
• 2009

Type I interferons (IFNs) are critical mediators of the innate immune system to defend viral infection. Interferon regulatory factor (IRF) and signal transducer and activator of transcription (STAT) play critical roles in type I IFN production in response to viral infection. Luteolin is natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anti-carcinogenic effects. However, the mechanism of action and impact of luteolin on innate immunity is still unknown. In this study, we examined the effects of luteolin on the lipopolysacchride (LPS)-induced inflammatory responses. Luteolin inhibited Type I IFNs expression of mRNA and increased interleukin(IL)-10 expression of mRNA. Next, we examined the protective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action didn't cause a significant reduction of Type I IFNs than LPS-induced luteolin pretreatment. Pretreatment of luteolin inhibited the level of IRF-1, and IRF-7 mRNA and the nuclear translocation of IRF-3. Also, luteolin reduced the activation of STAT - 1, 3. Theses results suggest that luteolin inhibits LPS-induced the production of Type I IFNS by both IRFs and STATs not IL-10 and may be a beneficial drug for the treatment of inflammatory disease.

• The Korean Journal of Physiology and Pharmacology
• /
• v.17 no.6
• /
• pp.547-551
• /
• 2013

We recently reported a Philyra pisum lectin (PPL) that exerts mitogenic effects on human lymphocytes, and its molecular characterization. The present study provides a more detailed characterization of PPL based on the results from a monosaccharide analysis indicating that PPL is a glycoprotein, and circular dichroism spectra revealing its estimated ${\alpha}$-helix, ${\beta}$-sheet, ${\beta}$-turn, and random coil contents to be 14.0%, 39.6%, 15.8%, and 30.6%, respectively. These contents are quite similar to those of deglycosylated PPL, indicating that glycans do not affect its intact structure. The binding properties to different pathogen-associated molecular patterns were investigated with hemagglutination inhibition assays using lipoteichoic acid from Gram-positive bacteria, lipopolysaccharide from Gram-negative bacteria, and both mannan and ${\beta}$-1,3-glucan from fungi. PPL binds to lipoteichoic acids and mannan, but not to lipopolysaccharides or ${\beta}$-1,3-glucan. PPL exerted no significant antiproliferative effects against human breast or bladder cancer cells. These results indicate that PPL is a glycoprotein with a lipoteichoic acid or mannan-binding specificity and which contains low and high proportions of ${\alpha}$-helix and ${\beta}$-structures, respectively. These properties are inherent to the innate immune system of P. pisum and indicate that PPL could be involved in signal transmission into Gram-positive bacteria or fungi.

• Korean Journal of Pharmacognosy
• /
• v.41 no.2
• /
• pp.115-121
• /
• 2010

The present study was designed to explore an immunostimulating activity of crude extracts of Macrolepiota procera, and a combination therapy of cisplatin and Macrolepiota procera extracts which can potentiate the anti-cancer activity of cisplatin. For these, water extraction of Macrolepiota procera were performed at $4^{\circ}C$(MPE-4) and $100^{\circ}C$(MPE-100). In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous administration of MPE ($80-2,000{\mu}g$/mouse) inhibited tumor metastasis compared with tumor control. Peritoneal macrophages stimulated with MPE produced IL-12 as well as induced tumoricidal activity. In an analysis of NK-cell activity, i.v. administration of MPE ($200{\mu}g$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin ($20{\mu}g$) and MPE ($100{\mu}g$) exhibited prolongation of lifespan in colon26-M3.1 tumor bearing mouse. These results suggested that MPE stimulate immune system non-specifically and application as adjuvant in cancer treatment.

• Journal of Microbiology and Biotechnology
• /
• v.24 no.9
• /
• pp.1269-1279
• /
• 2014

Xanthomonas oryzae pv. oryzae (Xoo) strains are plant pathogenic bacteria that can cause serious blight of rice, and their virulence towards plant host is complex, making it difficult to be elucidated. Caenorhabditis elegans has been used as a powerful model organism to simplify the host and pathogen system. However, whether the C. elegans is feasible for studying plant pathogens such as Xoo has not been explored. In the present work, we report that Xoo strains PXO99 and JXOIII reduce the lifespan of worms not through acute toxicity, but in an infectious manner; pathogens proliferate and persist in the intestinal lumen to cause marked anterior intestine distension. In addition, Xoo triggers (i) the p38 MAPK signal pathway to upregulate its downstream C17H12.8 expression, and (ii) the DAF-2/DAF-16 pathway to upregulate its downstream gene expressions of mtl-1 and sod-3 under the condition of daf-2 mutation. Our findings suggest that C. elegans can be used as a model to evaluate the virulence of Xoo phytopathogens to host.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.2
• /
• pp.145-153
• /
• 2018

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6409-6413
• /
• 2012

The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-$1{\beta}$, interleukin-8 and TNF-${\alpha}$ and apoptosis of THP-1 with PGN dose and time dependence. Moreover, in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-${\alpha}$-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.