• Parasites, Hosts and Diseases
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• v.52 no.5
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• pp.459-469
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• 2014

Entamoeba histolytica is a tissue-invasive protozoan parasite causing dysentery in humans. During infection of colonic tissues, amoebic trophozoites are able to kill host cells via apoptosis or necrosis, both of which trigger IL-8-mediated acute inflammatory responses. However, the signaling pathways involved in host cell death induced by E. histolytica have not yet been fully defined. In this study, we examined whether calpain plays a role in the cleavage of pro-survival transcription factors during cell death of colonic epithelial cells, induced by live E. histolytica trophozoites. Incubation with amoebic trophozoites induced activation of m-calpain in a time- and dose-dependent manner. Moreover, incubation with amoebae resulted in marked degradation of STAT proteins (STAT3 and STAT5) and NF-${\kappa}B$ (p65) in Caco-2 cells. However, $I{\kappa}B$, an inhibitor of NF-${\kappa}B$, was not cleaved in Caco-2 cells following adherence of E. histolytica. Entamoeba-induced cleavage of STAT proteins and NF-${\kappa}B$ was partially inhibited by pretreatment of cells with a cell-permeable calpain inhibitor, calpeptin. In contrast, E. histolytica did not induce cleavage of caspase-3 in Caco-2 cells. Furthermore, pretreatment of Caco-2 cells with a calpain inhibitor, calpeptin (but not the pan-caspase inhibitor, z-VAD-fmk) or m-calpain siRNA partially reduced Entamoeba-induced DNA fragmentation in Caco-2 cells. These results suggest that calpain plays an important role in E. histolytica-induced degradation of NF-${\kappa}B$ and STATs in colonic epithelial cells, which ultimately accelerates cell death.

• The Plant Pathology Journal
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• v.24 no.2
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• pp.101-111
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• 2008

The fungal genus Alternaria is comprised of many saprophytic and endophytic species, but is most well known as containing many notoriously destructive plant pathogens. There are over 4,000 Alternaria/host associations recorded in the USDA Fungal Host Index ranking the genus 10th among nearly 2,000 fungal genera based on the total number of host records. While few Alternaria species appear to have a sexual stage to their life cycles, the majority lack sexuality altogether. Many pathogenic species of Alternaria are prolific toxin producers, which facilitates their necrotrophic lifestyle. Necrotrophs must kill host cells prior to colonization, and thus these toxins are secreted to facilitate host cell death often by triggering genetically programmed apoptotic pathways or by directly causing cell damage resulting in necrosis. While many species of Alternaria produce toxins with rather broad host ranges, a closely-related group of agronomically important Alternaria species produce selective toxins with a very narrow range often to the cultivar level. Genes that code for and direct the biosynthesis of these host-specific toxins for the Alternaria alternata sensu lato lineages are often contained on small, mostly conditionally dispensable, chromosomes. Besides the role of toxins in Alternaria pathogenesis, relatively few genes and/or gene products have been identified that contribute to or are required for pathogenicity. Recently, the completion of the A. brassicicola genome sequencing project has facilitated the examination of a substantial subset of genes for their role in pathogenicity. In this review, we will highlight the role of toxins in Alternaria pathogenesis and the use of A. brassicicola as a model representative for basic virulence studies for the genus as a whole. The current status of these research efforts will be discussed.

• BMB Reports
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• v.51 no.5
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• pp.219-224
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• 2018

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2004.10a
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• pp.65-67
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• 2004

During initial interactions of bacteria with their host plants, most plants recognize the bacterial infections and repel the pathogen by plant defense mechanism. The most active plant defense mechanism is the hypersensitive response (HR) which is the localized induced cell death in the plant at the site of infection by a pathogen. A primary locus induced in gram-negative phytopathogenic bacteria during this initial interaction is the Hrp locus. The Hrp locus is composed of a cluster of genes that encodes the bacteral Type 111 machinery that is involved in the secretion and translocation of effector proteins to the plant cell. DNA sequence analysis of hrp gene in phytopathogenic bacteria has revealed a Hrp pathogenicity is]and (PAI) with a tripartite mosaic structure. For many gram-negative pathogenic bacteria, colonization of the host's tissue depends on the type III protein secretion system (TTSS) which secrets and translocates effector proteins into the host cell. Effectors can be divided into several groups including broad host range effectors, host specific effectors, disease specific effectors, and effectors inhibit host defenses. The role of effectors carrying LRR domain in plant resistance is very elusive since most known plant resistance gene carry LRR domain. Host specific effectors such as several avr gene products are involved in the determination of the host specificity. Almost all the phytopathogenic Xanthomonas spp. carry avrBs1, avrBs2, and avrBs3 homologs. Some strains of X. oryzae pv. oryzae carry more than 10 copies of avrBs3 homologs. However, the functions of all those avr genes in host specificity are not characterized well.;

• Parasites, Hosts and Diseases
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• v.49 no.2
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• pp.177-180
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• 2011

Entamoeba histolytica is an enteric tissue-invading protozoan parasite that can cause amebic colitis and liver abscess in humans. E. histolytica has the capability to kill colon epithelial cells in vitro; however, information regarding the role of calpain in colon cell death induced by ameba is limited. In this study, we investigated whether calpains are involved in the E. histolytica-induced cell death of HT-29 colonic epithelial cells. When HT-29 cells were co-incubated with E. histolytica, the propidium iodide stained dead cells markedly increased compared to that in HT-29 cells incubated with medium alone. This pro-death effect induced by ameba was effectively blocked by pretreatment of HT-29 cells with the calpain inhibitor, calpeptin. Moreover, knockdown of m- and ${\mu}$-calpain by siRNA significantly reduced E. histolytica-induced HT-29 cell death. These results suggest that m- and ${\mu}$-calpain may be involved in colon epithelial cell death induced by E. histolytica.

• Biomedical Science Letters
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• v.29 no.3
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• pp.178-183
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• 2023

Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of non-killing (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.

• The Plant Pathology Journal
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• v.28 no.3
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• pp.322-329
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• 2012

This study was conducted to investigate host and non-host disease resistances of kimchi cabbage plants to bacterial infection. Kimchi cabbage leaves responded differently to infections with a virulent strain of Xanthomonas campestris pv. campestris (Xcc) 8004 and two strains (85-10 and Bv5-4a.1) of non-host bacteria X. campestris pv. vesicatoria (Xcv). Non-host bacteria triggered a rapid tissue collapse of the leaves showing as brown coloration at the infected sites, highly increased ion leakage, lipid peroxidation and accumulation of UV-stimulated autofluorescence materials at the inoculated sites. During the observed interactions, bacterial proliferations within the leaf tissues were significantly different. Bacterial number of Xcc 8004 progressively increased within the inoculated leaf tissues over time, while growths of two non-host bacteria Xcv strains were distinctly limited. Expressions of pathogenesis-related genes, such as GST1, PR1, BGL2, VSP2, PR4 and LOX2, were differentially induced by host and non-host bacterial infections of X. campestris pathovars. These results indicated that rapid host cellular responses to the non-host bacterial infections may contribute to an array of defense reactions to the non-host bacterial invasion.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.37.1-37.15
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• 2020

Mycobacterium tuberculosis (Mtb) is an etiologic pathogen of human tuberculosis (TB), a serious infectious disease with high morbidity and mortality. In addition, the threat of drug resistance in anti-TB therapy is of global concern. Despite this, it remains urgent to research for understanding the molecular nature of dynamic interactions between host and pathogens during TB infection. While Mtb evasion from phagolysosomal acidification is a well-known virulence mechanism, the molecular events to promote intracellular parasitism remains elusive. To combat intracellular Mtb infection, several defensive processes, including autophagy and apoptosis, are activated. In addition, Mtb-ingested phagocytes trigger inflammation, and undergo necrotic cell death, potentially harmful responses in case of uncontrolled pathological condition. In this review, we focus on Mtb evasion from phagosomal acidification, and Mtb interaction with host autophagy, apoptosis, and necrosis. Elucidation of the molecular dialogue will shed light on Mtb pathogenesis, host defense, and development of new paradigms of therapeutics.

• Parasites, Hosts and Diseases
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• v.46 no.4
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• pp.217-221
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• 2008

Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.463-468
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• 2012

Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic ${\beta}$-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic ${\beta}$-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic ${\beta}$-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic ${\beta}$-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic ${\beta}$ cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.