Muhammad Rafi
Professor Chuck Fink
Biology 4100
10 March, 15
Interleukin 6 Interleukin 6 is a type of protein that plays a role in immune system by its multifunctional acts of pro-inflammatory and anti-inflammatory response. It is produced by T-cells and macrophages. Interleukin 6 is encoded by “IL-6” gene in humans. IL-6 is type of myokine that stimulates immune response during infection and after trauma. IL-6 works by binding to two cell surface receptors, IL-6Ra (low-affinity specific) and gp130 (high-affinity converter) respectively (Crystal Structure…). In late 1960s, T-cells essential role of being involved in antibody production was reported. Dr. Tadamitsu Kishimoto discovered the activity of IL-6 in early 1970s. The factors
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The gene promoter contains elements that are induced by stimuli; glucocorticoid and cAMP. The protein itself is located in extracellular regions in the body. The IL-6 protein usually operates by classical and trans-signaling pathways to process expression. Following image shows the difference between two types of signal pathways. (The pro- and anti-inflammatory…) One of the many roles of IL-6 includes the profound effects on B-cells. It supports B-cell growth by the production of antibodies and promoting plasma cell differentiation. The trans-signaling of IL-6 plays an important role in chronic inflammation (Inhibition of Classic…). In acute inflammation, IL-6 is released along with neutrophil accumulation by proinflammatory cytokines. The chemokine (IL-8) makes neutrophils promote the IL-6R and leads to differential regulation of chemokine production. This results in the production of MCP-1 and IL-8 reduction, which favors the monocyte accumulation. This trans-signaling also promotes the leukocyte accumulation. In contrary, the IL-6 also saves T-cells from apoptosis leading to inflammatory cell infiltrate. This positive feedback of trans-signaling releases IL-6 and plays a role in propagating chronic inflammation. The trans-signaling of IL-6 also has its implications in autoimmune diseases. In Crohn’s disease, the IL-6 inhibits Na2+/K+ATPase and protects
Inflamed tissues from Ulcerative Colitis (UC) patients show increased oxidative and nitrosative damage, leading to accumulation of mutations and dysplastic progression27,28. Infiltrating leukocytes from these patients have increased ROS production in basal conditions and in response to different ligands29. Since TLR4 mediates ROS production in leukocytes22, it is easy to speculate that immune cells drive pro-tumorigenic effects of TLR4. However, bone marrow-transfer experiments in our lab demonstrate that non-immune TLR4 participates in development of neoplasia8. Furthermore, we have shown that epithelial TLR4 activation predisposes to colitis and CAC6. To understand the role of epithelial TLR4 in neoplasia, our research has focused on the
A group of low-molecular-weight peptides that are active at low concentrations better known as Cytokines, bind to certain receptors and produce autocrine, paracrine, and endocrine. Chemokines peptides attract inflammatory cells. Therefore, Cytokine and chemokine produce and attract T-cell infiltration. TH-1 cells in Crohn's disease patients increase the inflammatory response (Lashner,2013). Prognosis of Crohn's varies among patients. Patients may have long periods of remission and possibly become free of symptoms for years. Although, there are treatments for Crohn's disease it is not possible to know if treatment has helped or when symptoms will return. Regardless of Crohn's disease reoccurring various times through one's lifetime, patients are able to hold jobs, raise families and function in society the same way a healthy individual would (Prognosis of Crohn's
Inflammatory Bowel Disease (IBD) is a chronic and relapsing gastrointestinal condition currently affecting a total of about 28 million people worldwide (cite). Although it is not considered a fatal condition, painful and disabling symptoms can have a profound detrimental effect on patients’ quality of life. Current understandings behind the etiology of IBD emphasize genetic predispositions to gastrointestinal immune system imbalances. However, pathophysiological understandings of IBD seem to be limited as explanatory tools given the distribution of IBD cases in industrialized and non-industrialized countries. Therefore, this paper will provide an overview of the biological aspect of IBD alongside significant environmental drivers of the
The patient was presented to me with diagnosed crohn’s disease, in remission stage. Crohn’s disease is a chronic inflammatory disease of the intestines. Primarily, it causes ulcerations in the small and large intestines but has been seen to affect the digestive system anywhere from the oral cavity to the anus. The disease has no known cure but once the disease begins it proceeds to vary between periods of inactivity (remission) and activity (relapse). The cause of crohn’s disease is unknown but from research it is suspected that infections by certain bacterium could contribute to the disease. The activation of the immune system in the intestines is seen to be of importance to patients with crohn’s. The immune system causes inflammation within the tissues where it occurs. In normal cases the activation occurs when the body is exposed to harmful invaders. With patients with crohn’s disease the immune system is abnormally activated in the absence of any invader, thus resulting in chronic inflammation and ulceration as seen in the figure below. The disease causes abscesses and a cobble stone appearance to the infected area in the body, this infection causes the immune system to activate in an inflammatory response.
JFK makes it clear that every citizen should do what is right not only to them, but for the benefit of the country. Kennedy uses a quote from the bible to support his ideas of making the world unite, and disengage in their disagreements and to flourish with one another. Furthermore in 1960, the cold war was occurring and in Kennedy’s inaugural address, Kennedy warns about the cold war and how America should aim for peace with all nations in the world. Throughout his speech, Kennedy has a patriotic and hopeful tone.
This prevents the release of the inflammatory factors which cause Crohn’s disease; however it also prevents the intended effects of the cell, such as inducing cell apoptosis, and inhibiting viral replication. Due to these side effects, anti-TNF-α treatment can result in an increased risk of cancer, infection and fungal infections. Furthermore, although effective in most patients, 30% of people who receive this treatment do not respond and continue to show symptoms from Crohn’s [6]. This suggests that TNF-α is not the only cause of the disease, adding to the complexity of the
Immunology basically involves understanding the immune system and how it responds to various disease conditions. the immune system consists of a number of components. Traditionally, it is divided into humoral and cellular immune responses. It can also be distinguished into innate and adaptive immunity. The innate immunity can discriminate between normal tissues , self and newly encountered non-self-proteins while the adaptive immunity is the more complex system aimed at the eradication of intracellular pathogens. To do this, antigen derived from such pathogens that are often new to the host organism, need to be recognised by receptor-bearing specialised immune cells which respond to a complex system of stimulatory and costimulatory signals. Better understanding of the human immune system has led to the identification of a number of tumor-associated antigens in the 1980s and the development of various immunotherapeutic approaches. In recent years, identification of the specific antigenic MHC class I epitopes, advancements in genetic engineering, gene delivery, and cell-based therapeutic approaches allowed development of the novel immunotherapeutics.
Should the Death Penalty still be an option or only life in prison? This is the question at issue that the writer, Kyle Gibson(Heritage Foundation research fellow for the Center for Data Analysis), debates in the article, “ Death Penalty Repeal: It’s necessary to use Capital Punishment in a Free World”. On June 23, 2013 Gibson explains that Capital Punishment is a right and is important in society. He provides evidence on why Capital Punishment is important and how it is a free right of all citizens. His purpose is to show readers why the death penalty is important in order to convince readers to support and not oppose the death penalty.
Crohn’s Disease is an intestinal disease first discovered by and named after Dr. Burrill B. Crohn, “who first described the disease in 1932 along with colleagues Dr. Leon Ginzburg and Dr. Gordon D. Oppenheimer.” (Foundation, 2015) Konkel (2015) refers to this disease as belonging “to a group of conditions called inflammatory bowel diseases (IBD)” (Konkel, 2015) CD is
Studies have revealed that the P2X7 receptor may hold some of these answers (Ferrari et al. 1997), (Perregaux and Gabel, 1998). P2X7 is said to be a key mediator in the activation and secretion of the interleukin-1 family of cytokines. Perhaps the two most well established are the mechanisms involved with the maturation and release of IL-1β and IL-18. Muñoz-Planillo et al. (2013) suggests that rapid K+ efflux acts as a co-signal alongside activation of toll-like receptors via pathogen-associated molecular patterns (PAMPs). These two signals combined are said to initiate the assembly of the NLRP3 inflammasome. Whilst the signal received through toll-like receptors is responsible for the synthesis of inflammasome components and inactive forms of IL-1β and IL-18, the second signal received through rapid K+ efflux influences the assembly of the inflammasome itself leading to the activation of caspase-1. Caspase-1 processes and activates pro-IL-1β and pro-IL-18
Interleukins are a type of cytokines and play a vital role in nearly all aspects of inflammation and immunity. They were first seen to be expressed by leukocytes. Interleukin is a term that has been used to describe a group of cytokines with complex immunomodulatory functions – including maturation, cell proliferation, migration and adhesion. They also play an important role in immune cell differentiation and activation. Interleukins initiate a response by binding to like receptors located on the surface of cells; they function in an autocrine or paracrine fashion, rather than an endocrine signal, which is more common with steroidal and amino acid-derived and hormones. The response to these cytokines depends on several different factors such
Abstract: Selectins are carbohydrate-binding proteins that play a vital role in inflammatory responses. These proteins are involved in the homing of leukocytes and have been implicated in numerous diseases, including autoimmune diseases such as multiple sclerosis as well as various form of cancer. In addressing the role of selectins in autoimmune diseases, it has been found that they involved in the trafficking of immune cells to secondary lymphoid organs under normal conditions as well as to peripheral tissues during inflammation. Precise selectin–ligand interactions facilitate the recruitment of distinct immune cell subpopulations in specific target organs during autoimmune diseases. Additionally, selectins (and their ligands) are also vital for homeostasis and immune cell activation. Tissue-specific, selectin antagonists are fairly promising new therapeutic approaches for the treatment of autoimmune and inflammatory diseases, however, a more precise mechanism for selectin leukocyte targeting must be uncovered first. Selectins also have been found to translate their roles in cellular adhesion to metastatic progression when the correct ligand is present. Though selectins have been identified as potential facilitators of metastasis, they have not been studied as drug targets for treating cancer progression and metastasis. However, targeting selectins as a cancer metastasis treatment could prove very successful as seen from initial positive clinical findings regarding heparin
For instance, Crohn’s disease(CD) is a chronic relapsing inflammatory bowel disease (IBDs), which affect the various areas of GI tract (from mouse to anus) and lead to abdominal cramps, weight loss, diarrhea, fever and the other symptom. According to the survey, Crohn’s disease was found to be more common in developed industrialized countries than less developed tropical countries because people who lived in developed areas have less chance of exposure to helminthes. Therefore, although the cause of Crohn’s disease is not fully understood, but it is consider to be related to environmental, genetic factor and autoimmune reaction. Medically speaking, Crohn’s disease is classified as an autoimmune disorder. Usually, there are many harmless and
Tumour Necrosis Factor (TNF) also plays a central role in the pathogenesis of IBD as it has been shown to exert various
OIS is emerging as a potent cancer-protective response to oncogenic events, serving to eliminate early neoplastic cells from the proliferative pool. Kuilman et al. (2008) reported a unique role of interleukin-6 (IL-6) in OIS of cancer cells. Using combined genetic and bioinformatic analysis, they found that OIS was linked specifically to the activation of an inflammatory transcriptome. Induced genes included IL-6, which upon secretion by senescent cells acted mitogenically in a paracrine fashion (Kuilman 2008). IL-6 was also required for the execution of OIS, but in a cell-autonomous fashion. Its depletion caused the inflammatory network to collapse and abolished senescence entry and maintenance. They also demonstrated that C/EBPβ cooperated with IL-6 to amplify the activation of the inflammatory network, including IL-8. In human colon adenomas, IL-8 specifically colocalized with arrested, p16INK4a-positive epithelium. They proposed a model in which the context-dependent cytostatic and pro-mitogenic functions of interleukins contribute to connect senescence with an inflammatory phenotype and cancer. The role of role of IL-6 in OIS has been confirmed by later studies