Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.36
no.6
/
pp.481-489
/
2010
Introduction: TLR-5, a member of the toll-like receptor (TLR) family, is a element of the type I transmembrane receptors, which are characterized by an intracellular signaling domain homolog to the interleukin-1 receptor. These receptors recognize microbial components, particularly bacterial flagellin. All-trans retinoic acid (atRA, tretinoin), a natural metabolite of vitamin A, acts as a growth and differentiation factor in many tissues, and is also needed for immune functions. In this study, THP-1 human macrophage-monocytes were used to examine the mechanisms by which atRA regulated the expression of TLR-5. Because the molecular mechanism underlying this regulation at the transcriptional level is also unclear, this study examined which putative transcription factors are responsible for TLR-5 expression by atRA in immune cells. Materials and Methods: This study examined whether atRA induces the expression of TLR-5 in THP-1 cells using reverse transcription-polymerase chain reaction (RT-PCR), and which transcription factors are involved in regulating the TLR-5 promoter in RAW264.7 cells using a reporter assay system. Western blot analysis was used to determine which signal pathway is involved in the expression of TLR-5 in atRA-treated THP-1 cells. Results: atRA at a concentration of 10 nM greatly induced the expression of TLR-5 in THP-1 cells. Human TLR-5 promoter contains three Sp-1/GC binding sites around -50 bp and two NF-kB binding sites at -380 bp and -160 bp from the transcriptional start site of the TLR-5 gene. Sp-1/GC is primarily responsible for the constitutive TLR-5 expression, and may also contribute to NF-kB at -160 bp to induce TLR-5 after atRA stimulation in THP-1 cells. The role of NF-kB in TLR-5 expression was further confirmed by inhibitor pyrrolidine dithiocarbamate (PDTC) experiments, which greatly reduced the TLR-5 transcription by 70-80%. Conclusion: atRA induces the expression of the human TLR-5 gene and NF-kB is a critical transcription factor for the atRA-induced expression of TLR-5. Accordingly, it is conceivable that retinoids are required for adequate innate and adaptive immune responses to agents of infectious diseases. atRA and various synthetic retinoids have been used therapeutically in human diseases, such as leukemia and other cancers due to the antiproliferative and apoptosis inducing effects of retinoids. Therefore, understanding the molecular regulatory mechanism of TLR-5 may assist in the design of alternative strategies for the treatment of infectious diseases, leukemia and cancers.
Lysozyme is known as a key substance of the innate immunity and have antibacterial effect in the mucosal tissues, especially middle ear. Aquaporin (AQP) functions as water movement in the tissue and has been expected to be participated in the inflammatory responses. In the present study, we investigated to reveal association of lysozymes and AQPs in otitis media. The gene expression of lysozyme genes, homo sapiens lysozyme (hLYZ), homo sapiens lysozyme M (hLYZ M), and homo sapiens lysozyme G like-2 (hLYGH), and AQP genes (AQP 0 - AQP 12) were measured from postauricular skin, mastoid mucosa, inflamed mastoid mucosa, and middle ear mucosa. The hLYZ, hLYZ M and hLYGH gene were expressed in mastoid mucosa, inflamed mastoid mucosa, middle ear mucosa. Of AQP genes, all AQP gene except AQP 3 gene were expressed in the tissue of middle ear. Among them, AQP 4, AQP 8, AQP 9, AQP 10, AQP 11 and AQP 12 were highly expressed in the inflamed mastoid mucosa and normal mastoid mucosa (P<0.001). Interestingly, expression levels of AQP 4, AQP 9, and AQP 12 gene were significantly higher in the inflamed mastoid mucosa compared to normal middle ear mucosa (P<0.05). These results suggest that lysozyme and AQPs could be associated with inflammatory response in the middle ear.
The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.
Allergic diseases have increased over the past several decade worldwide including developing countries. Allergic inflammatory responses are caused by Th (T helper)2 immune responses, triggered by allergen ingestion by antigen presenting cells such as dendritic cells (DCs). Intestinal microorganisms control the metabolism and physiological functions of the host, contribute to early immune system maturation during the early life, and homeostasis and epithelial integrity during life. Bifidobacteria have strain-specific immunostimulatory properties in the Th1/Th2 balance, inhibit TSLP (thymic stromal lymphopoietin) and IgE expression, and promote Flg (Filaggrin) and FoxP3 (Treg) expression to alleviate allergies. In addition, unmethylated CpG motif ODN (oligodeoxynucleotides) is recognized by TLR (toll-like receptors)9 of B cells and plasmacytoid dendritic cells (pDCs) to induce innate and adaptive immune responses, while the butyrate produced by Clostridium butyricum activates the GPR (G-protein coupled receptors)109a signaling pathway to induce the expression of anti-inflammatory gene of pDCs, and directly stimulates the proliferation of thymically derived regulatory T (tTreg) cells through the activation of GPR43 or inhibits the activity of HADC (histone deacetylase) to differentiate naive $CD4^+$ T cells into pTreg cells through the histone H3 acetylation of Foxp3 gene intronic enhancer.
A review of this literature and discussions reveal a development of ideas concerning the elements of nursing models. The elements of a nursing model are the nurses view of the human being, nursing's goal, and nursing activities. It has long been recognized that human beings, at one time or another, require nursing care. Varieties of literature were reviewed in regard to the human being as recipient of nursing care through the theory development in nursing. Florence Nightingale initiated the modern era of nursing and described more clearly man as the recipient of nursing care. She looked at man as responding to the laws of nature whether the person was healthy or sick. Henderson added to Nightingale's concept of man , the recipient of nursing care by emphasizing that man is a whole, complete, and independent being. Her view is further specified by her enumeration of the activities the human being must perform. Johnson has developed a very comprehensive view of man as the recipient of nursing care. Man is a behavioral system which has a tendency to achieve and maintain stability in patterns of functioning. Like Nightingale, Johnson sees that similar patterns occur in both health and illness. Johnson postulates that the whole behavioral system of the human is composed of eight sub-systems: affiliative, achievement, aggressive, dependency, eliminative, ingestive, restorative, sexual. Roger's main contribution to the development of nursing models was her emphasis upon unitary man. She pointed out that man is a unified whole, possessing his own integrity and manifesting characteristics that“are more than and different from the sum of his parts.”Rogers focuses on the life processes of the human and points out that these processes have the following characteristics. Wholeness, openness, unidirectionality, pattern and organization, sentence, and thought. According to Roy, man is a biopsychosocial being in constant interaction with a changing environment. To cope with this changing environment, man has certain innate and acquired mechanisms. Man's ability to respond positively or to adapt, depends upon the degree of the change taking place and the state of the person coping with the change. When she analyzes man as an adaptive organism she further describes man as being composed of four adaptive modes: physiological needs, self-concept, role function, and interdependence. Based on the literary review through the theory development in nursing, general approach by a unified nursing model to a view of the recipient of nursing care may be stated as follows: Man is a unified whole composed of subsystems with a flexible and normal line of defense; his internal regulating mechanisms help him to cope with a changing environment; he functions by the principles of homeodynamics.
Vitamin D is a fat-soluble vitamin helps to retain calcium and phosphorus but also has shown to affect immune regulation and homeostasis. In humans, vitamin D3 and vitamin D2 and their metabolite has intensively studied in both innate and adaptive immune system that they are important to regulate overwhelmed inflammation. The vitamin D receptor is a nuclear hormone receptor which regulate various downstream target gene expressions as a transcription factor related to metabolism, immune regulation, etc. Vitamin D deficiency is a high-risk factor for inflammatory diseases like autoimmune disease and allergy. In addition, reduced vitamin D seem to correlate with susceptibility to the virus infection such as HIV and COVID-19. In this review, we will summarize up-to-date vitamin D's role in various immune cells, immune regulatory functions during autoimmune, allergic, and infectious diseases. We will also discuss about vitamin D supplement effects in human trial studies for COVID-19.
Jeungsan, Kang Il-Sun (hereafter, Jeungsan)'s perspective on divine beings can be characterized by the philosophical notion of divinity, which recognizes a variety of divine entities. Jeungsan insisted that all things embrace divine entities. Furthermore, he claimed that the backgrounds of all incidents were influenced by these gods. Jeungsan thought that the universe consists of the heavenly realm, the earthly realm and the underground realm. He insisted that there were many gods in each realm. And Jeungsan defined his times as the era of divine beings, which meant that the age was a time for divine beings to actively interact with one another and take the lead in world affairs. Divine beings were briskly involved in human affairs and could either reciprocate gratitude or attain revenge. They were also divine beings that could change the acts and perception of humans as well as judge human acts. However, Jeungsan predicted that by the time the paradisiacal land of immortals was established in the Later World, divine beings would instead run errands for humans. In addition, he forecast that divine beings would be entities likely to harbor grievances just like humans, yet they would ultimately become perfected beings in the Later World. Jeungsan further suggested a multitude of various concepts such as the mutual relationship wherein the realm of divine beings and the realm of humanity interrelate with each other, the mutual responses and functions between them, mutual itineration, co-existence, and the homogeneity of divine beings and humans, which described how both have the same innate characteristics. Jeungsan proposed the concept that 'Divinity is an existential state experienced after one's death." In this regard, he is the one who formulated a new perspective of divinity. Moreover, Jeunsan stressed the immortality of humans (continuity or eternality) and the co-existence of divine beings and humans. He emphasized that divinity is intrinsically immanent and the realm of divine beings has a hierarchical system that maintains order and is akin to that of the human realm. Jeungsan recognized a revolutionary change and perspective based on humanity by suggesting a unique view of humanity. In other words, he was a religious figure who introduced an ingenious view of divinity and dramatically transformed this pattern of reasoning. In conclusion, Jeungsan re-interpreted traditional views of divinity in Korea and systemized them into a new concept of divinity in an ingenious way.
This study aims to elucidate the origin and yield of life and its characteristics and purpose in Daesoon Thought. Thereby, Taegeuk (the Great Ultimate) and Sangje (the Supreme God) have been deemed the source and ontology of life. The structure of each living creature is explained through reason (理), energy (氣) and spirit (神). In addition, through vital reason and living energy, the purpose of life makes the realization of the benevolent characteristics of life possible through the mind of Sangje. This line of research is unique among currently available research views of life as it perceives the spirit to be an ontological entity with functions and interactive engagement. By way of contrast, prior research suggests that spirit is life itself and includes it in the category of life and death. The Daesoon view of life is unique in that it is somewhat influenced by ontology and developmental theories from Confucianism, yet the concept of divine beings suggests a humanistic Sangje, who presides over the Great Ultimate. The realization of reason in this model is rather thought-provoking. Humans, just like other living things, are born with vital essence and function and interact as a main source to preside over the innate spirits inside themselves. Humans take responsibility for a certain sphere in the Three Realms that make up the world. They are also recognized as a significant feature in the world. Such an idea in Daesoon Thought depicts that 'the enshrinement of spirit into human being (神封於人),' follows Heaven and Earth. This is done to rectify humans in order to meet the needs of the universe and ultimately establish the era of the enshrinement of spirits into human beings. As for humanity, this possibility exists because of the spirits contained within their inner-selves. When cultivating oneself, humans and outer spirits actively interact with each other. This is likely to cause changes in a human's constitution and characteristics. In the end, one can be enshrined with corresponding divine beings according to one's degree of cultivation. Humans are born through the command of Sangje and the accomplishments of their ancestors as well as the energy of the universe. Present day humans encounter the era of human nobility and the era of humankind's divine salvation. Thereby, the purpose of human life is to contribute to the universe. To achieve this goal, the most important thing is to wholly realize that one's nature and reason were endowed by Heaven, which emerged from virtuous conduct in society. This is also akin to the movement of reason in Jeungsanist Thought. Sangsaeng (mutual beneficence) among oneself and others and between human beings and divine beings can be completed through the resolution of grievances for mutual beneficence and the grateful reciprocation of favors for mutual beneficence. If one accomplishes the perfected state of one's own nature and reveals it wholly, then one will be fully able to interact with spirits and reach the state of the human nobility.
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