The role of pro-inflammatory cytokines in the pathogenesis and progression of neoplasms

Cytokines play an important role in the functioning of the immune system. Studies have reported an increased secretion of inflammatory cytokines by the neoplasms. Inflammation plays a role in the pathogenesis of various diseases; it is also a risk factor for the development and progression of a neoplasm, as exemplified by the development of cancer in the region of the head and neck in response to chronic inflammation caused by irritants present, e.g. in cigarette smoke. Cytokines (IL-1 beta, IL-6, TNF, IL-8, IL-17), which take part in the inflammatory response and are, therefore, strongly involved in the development of cancer. The combined action of cytokines produced by the neoplastic cells via multiple mechanisms, modulates cell response of the host immune system. Clinical observations suggest that cancer patients show a progressive disorder of the immune system, resulting in tumor progression. The mechanisms conducive to the weakening or lack of an immune response to neoplastic antigens contribute to the severity of the invasion of cancerous lesions. Although mechanisms that occur between tumor cells, the micro-environment of the tumor and immune cells of the host are not thoroughly known, previous research point to the importance of this interaction in oncogenesis, which may ultimately affect the prognosis.

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Enhancement of immune response against Bordetella spp. by disrupting immunomodulation

Scientific Reports ◽

10.1038/s41598-019-56652-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Monica C. Gestal ◽

Laura K. Howard ◽

Kalyan Dewan ◽

Hannah M. Johnson ◽

Mariette Barbier ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Cells ◽

Lymphoid Tissue ◽

Protective Immunity ◽

Inflammatory Cells ◽

Host Immune System ◽

Initial Growth ◽

Wild Type ◽

Sterilizing Immunity

AbstractWell-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the respiratory tract of mice, its natural host, but did increase activation of the inflammasome pathway, and recruitment of inflammatory cells. The mutant lacking btrS recruited many more B and T cells into the lungs, where they rapidly formed highly organized and distinctive Bronchial Associated Lymphoid Tissue (BALT) not induced by any wild type Bordetella species, and a much more rapid and strong antibody response than observed with any of these species. Immunity induced by the mutant was measurably more robust in all respiratory organs, providing completely sterilizing immunity that protected against challenge infections for many months. Moreover, the mutant induced sterilizing immunity against infection with other classical bordetellae, including B. pertussis and B. parapertussis, something the current vaccines do not provide. These findings reveal profound immunomodulation by bordetellae and demonstrate that by disrupting it much more robust protective immunity can be generated, providing a pathway to greatly improve vaccines and preventive treatments against these important pathogens.

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A pronounced uterine pro-inflammatory response at parturition is an ancient feature in mammals

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2017.1694 ◽

2017 ◽

Vol 284 (1865) ◽

pp. 20171694 ◽

Cited By ~ 11

Author(s):

Victoria L. Hansen ◽

Lauren S. Faber ◽

Ali A. Salehpoor ◽

Robert D. Miller

Keyword(s):

Immune System ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Immune Regulation ◽

Monodelphis Domestica ◽

Immune Gene ◽

Invasive Placenta ◽

Gene Transcripts ◽

Pro Inflammatory Cytokines

Regulating maternal immunity is necessary for successful human pregnancy. Whether this is needed in mammals with less invasive placentation is subject to debate. Indeed, the short gestation times in marsupials have been hypothesized to be due to a lack of immune regulation during pregnancy. Alternatively, the maternal marsupial immune system may be unstimulated in the absence of a highly invasive placenta. Transcripts encoding pro-inflammatory cytokines were found to be overrepresented in the whole uterine transcriptome at terminal pregnancy in the opossum, Monodelphis domestica . To investigate this further, immune gene transcripts were quantified throughout opossum gestation. Transcripts encoding pro-inflammatory cytokines remained relatively low during pre- and peri-attachment pregnancy stages. Levels dramatically increased late in gestation, peaking within 12 h prior to parturition. These results mirror the spike of inflammation seen at eutherian parturition but not at attachment or implantation. Our results are consistent with the role of pro-inflammatory cytokines at parturition being an ancient and conserved birth mechanism in therian mammals.

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Down Regulation Of IL-1β Secretion By Tgf-β1 In Macrophages Infected With Dengue Virus

10.1101/2021.02.03.429556 ◽

2021 ◽

Author(s):

Brenda Ramírez-Aguero ◽

Javier Serrato-Salas ◽

José Luis Montiel-Hernández ◽

Judith González-Christen

Keyword(s):

Immune Response ◽

Dengue Virus ◽

Inflammatory Cytokines ◽

Denv Infection ◽

Inhibitory Effect ◽

Microvascular Endothelium ◽

Infected Cells ◽

Tgf Β1 ◽

Pro Inflammatory Cytokines

AbstractSeveral pathogenic mechanisms have been linked to the severity of dengue virus infection, like viral cytotoxicity, underlying host genetics and comorbidities such as diabetes and dyslipidemia. It has been observed that patients with severe manifestations develop an uncontrolled immune response, with an increase in pro-inflammatory cytokines such as TNF, IL-1β, IL-8, IL-6 and chemokines that damage the human microvascular endothelium, and also in anti-inflammatory cytokines IL-4, IL-10 and TGF-β1. The role of TGF-β1 on dengue is not clear; few studies have been published, and most of them from patient sera data, with both protective and pathological roles have described. The aim of this study was to evaluate the ability of TGF-β1 to regulate the secretion of IL-1β in macrophages infected by DENV using THP-1 cells treated with recombinant TGF-β1 before or after DENV infection. By RT-PCR we did not observe a difference in IL-1β expression between infected cells pretreated with TGF-β1 and those that were not. However, secretion of IL-1β was reduced only in cells stimulated with TGF-β1 before infection, and not in those treated 2 hours post-infection. TGF-β1 receptor blockage with SB505124 inhibitor, prior to the addition of TGF-β1 and infection, abrogated the inhibitory effect of TGF-β1. Our results suggest that DENV could regulate the function of TGF-β1 on macrophages. This negative regulation of the TGF-β1 pathway could be used by DENV to evade the immune response and could contribute to the immunopathology.

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Moms, babies, and bugs in immune development

F1000Research ◽

10.12688/f1000research.12182.1 ◽

2017 ◽

Vol 6 ◽

pp. 2141

Author(s):

Katie Alexander ◽

Charles O. Elson

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Cells ◽

Mucosal Immunity ◽

The Other ◽

Primary Role ◽

Initial Development ◽

Immune Development ◽

The One

Bacteria and mammals have co-evolved with one another over millennia, and it has become impossible to interpret mucosal immunity without taking the microbiota into consideration. In fact, the primary role of the mucosal immune system is regulating homeostasis and the host relationship with the microbiota. Bacteria are no longer seen as simply invading pathogens, but rather a necessary component to one’s own immune response. On the one hand, the microbiota is a vital educator of immune cells and initiator of beneficial responses; but, on the other, dysbiosis of microbiota constituents are associated with inflammation and autoimmune disorders. In this review, we will consider recent advances in the understanding of how the microbiota influences host mucosal immunity, particularly the initial development of the immune response and its implications.

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Research progress on the role of sialic acid-binding immunoglobulin-like lectin 9 in various diseases

Trends in Immunotherapy ◽

10.24294/ti.v5.i2.1.1366 ◽

2021 ◽

Vol 5 (2.1) ◽

pp. 51

Author(s):

Ling Cao ◽

Xiaoliang Yuan

Keyword(s):

Sialic Acid ◽

Autoimmune Diseases ◽

Inflammatory Cytokines ◽

Immune Cells ◽

Immune Escape ◽

Research Progress ◽

Tumor Immune Escape ◽

Sialic Acid Binding ◽

Pro Inflammatory Cytokines

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a receptor that expresses on the surface of immune cells. It plays an important role in the body’s immune response. Increased expression of Siglec-9 has been reported in infectious diseases, autoimmune diseases and cancer. Pathogenic microorganism and tumor cells can inhibit the recognition and killing of immune cells by upregulating their own specific sialic acid and binding with Siglec-9 on the surface of host immune cells, and suppress the release of pro-inflammatory cytokines and promote the release of anti-inflammatory cytokines, eventually leading to immunosuppression, tumor immune escape and the like. However, the immunosuppressive function of Siglec-9 may be advantageous for diseases such as neutrophil asthma and autoimmune diseases. Therefore, further research on the mechanism of action of Siglec-9 is of great significance.

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The role of the immune system in tendon healing: a systematic review

British Medical Bulletin ◽

10.1093/bmb/ldz040 ◽

2020 ◽

Vol 133 (1) ◽

pp. 49-64 ◽

Cited By ~ 2

Author(s):

Emanuele Chisari ◽

Laura Rehak ◽

Wasim S Khan ◽

Nicola Maffulli

Keyword(s):

Systematic Review ◽

Immune Response ◽

Immune System ◽

Mast Cells ◽

Immune Cells ◽

Tendon Healing ◽

Risk Of Bias ◽

Cochrane Library ◽

Healing Response

Abstract Introduction The role of the immune system in tendon healing relies on polymorphonucleocytes, mast cells, macrophages and lymphocytes, the ‘immune cells’ and their cytokine production. This systematic review reports how the immune system affects tendon healing. Sources of data We registered our protocol (registration number: CRD42019141838). After searching PubMed, Embase and Cochrane Library databases, we included studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results. The PRISMA guidelines were applied, and risk of bias and the methodological quality of the included studies were assessed. We excluded all the articles with high risk of bias and/or low quality after the assessment. We included 62 articles assessed as medium or high quality. Areas of agreement Macrophages are major actors in the promotion of proper wound healing as well as the resolution of inflammation in response to pathogenic challenge or tissue damage. The immune cells secrete cytokines involving both pro-inflammatory and anti-inflammatory factors which could affect both healing and macrophage polarization. Areas of controversy The role of lymphocytes, mast cells and polymorphonucleocytes is still inconclusive. Growing points The immune system is a major actor in the complex mechanism behind the healing response occurring in tendons after an injury. A dysregulation of the immune response can ultimately lead to a failed healing response. Areas timely for developing research Further studies are needed to shed light on therapeutic targets to improve tendon healing and in managing new way to balance immune response.

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Immune and Inflammatory Responses to Stroke: Good Or Bad?

International Journal of Stroke ◽

10.1111/j.1747-4949.2008.00222.x ◽

2008 ◽

Vol 3 (4) ◽

pp. 254-265 ◽

Cited By ~ 44

Author(s):

P. A. McCombe ◽

S. J. Read

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Responses ◽

Inflammatory Responses ◽

Tissue Injury ◽

Therapeutic Option ◽

Regulatory Lymphocytes ◽

The Brain ◽

Pro Inflammatory Cytokines

Inflammatory and immune responses play important roles following ischaemic stroke. Inflammatory responses contribute to damage and also contribute to repair. Injury to tissue triggers an immune response. This is initiated through activation of the innate immune system. In stroke there is microglial activation. This is followed by an influx of lymphocytes and macrophages into the brain, triggered by production of pro-inflammatory cytokines. This inflammatory response contributes to further tissue injury. There is also a systemic immune response to stroke, and there is a degree of immunosuppression that may contribute to the stroke patient's risk of infection. This immunosuppressive response may also be protective, with regulatory lymphocytes producing cytokines and growth factors that are neuroprotective. The specific targets of the immune response after stroke are not known, and the details of the immune and inflammatory responses are only partly understood. The role of inflammation and immune responses after stroke is twofold. The immune system may contribute to damage after stroke, but may also contribute to repair processes. The possibility that some of the immune response after stroke may be neuroprotective is exciting and suggests that deliberate enhancement of these responses may be a therapeutic option.

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Ovarian cancer and inflammation. Part 1. Pro-inflammatory cytokines.

Progress in Health Sciences ◽

10.5604/01.3001.0012.1329 ◽

2018 ◽

Vol 8 (1) ◽

pp. 194-201

Author(s):

KM. Terlikowska ◽

MA. Strzyż-Skalij ◽

K. Kryński ◽

M. Osmólska ◽

Z. Łada ◽

...

Keyword(s):

Ovarian Cancer ◽

Immune Response ◽

Immune System ◽

Immune Responses ◽

Cause Of Death ◽

Inflammatory Cytokines ◽

Gynecologic Malignancies ◽

Cancer Tumor ◽

Cancer And Inflammation ◽

Pro Inflammatory Cytokines

Ovarian cancer is the most threatening cause of death among gynecologic malignancies and represents the fifth leading cause of death from all cancers for women. Research reveals that ovarian cancer patients exhibit significant immune responses against the tumor. In this review of the current literature chiefly the interaction of ovarian cancer tumor cells and the immune system is discussed. There is increasingly growing evidence that pro-inflammatory cytokines are involved in intricate complex of mechanisms responsible for tumorigenesis, and delicate balance between pro- and anti-inflammatory cytokines is critical for the antitumor host immune response.

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Formal modeling of the key determinants of Hepatitis C Virus (HCV) induced adaptive immune response network: An integrative approach to map the cellular and cytokine-mediated host immune regulations

10.7287/peerj.preprints.26456v1 ◽

2018 ◽

Author(s):

Ayesha Obaid ◽

Anam Naz ◽

Shifa Tariq Ashraf ◽

Faryal Mehwish Awan ◽

Aqsa Ikram ◽

...

Keyword(s):

Immune Response ◽

Hepatitis C Virus ◽

Immune System ◽

Hepatitis C ◽

Biological Data ◽

Signaling Networks ◽

Host Immune System ◽

Adaptive Immune ◽

Ifn Γ

Background. Hepatitis C Virus (HCV) is a major causative agent of liver infection leading to critical liver damage. In response to HCV, the improper regulation of host immune system leads to chronic infection. The host immune system employs multiple cell types, diverse variety of cytokine mediators and interacting signaling networks to neutralize the HCV infection. To understand the complexity of the interactions within the immune signaling networks, systems biology provides an efficient alternative approach. Integrating such approaches with immunology and virology helps to study highly complex immune regulatory networks within the host and presents a concise view of the whole system. Methods. Initially, a logic-based diagram is generated based on multiple reported interactions between immune cells and cytokines during host immune response to HCV. Furthermore, an abstracted sub-network is modeled qualitatively which consists of both the key cellular and cytokine components of the HCV induced immune system. Rene’ Thomas formalism is applied in the study to generate a qualitative model which requires only the qualitative thresholds and associated logical parameters generated via SMBioNet software in accordance with biological observations. Furthermore, the continuous dynamics of the model have been studied via Petri nets based analysis. Results. In the presence of NS5A protein of HCV, the behaviors of the Natural Killer (NK) and T regulatory (Tregs) cells along with cytokines such as IFN-γ, IL-10, IL-12 are predicted. The model also attempts to consider the viral strategies to circumvent immune response mediated by viral proteins. The state graph analysis enabled the prediction of paths leading to disease state. The most probable cycle is predicted based on maximum betweenness centrality. Furthermore, to study the continuous dynamics of the modeled network, a Petri net (PN) model was generated. The predictive ability of the model implicates the critical role of IL-12 over-expression in pathogenesis. This observation speculates that IL-12 has a dual role under varying circumstances and leads to varying disease outcomes. Conclusion. This model attempts to reduce the noisy biological data and captures a holistic view of the regulations amongst the key determinants of HCV induced adaptive immune responses. The observations warrant for further studies to elucidate the role of IL-12 under varying external and internal stimuli. Also, introducing diversion by therapeutic perturbation may divert the system from diseased paths to recovery by stabilizing the activation of IFN-γ producing NK cells. The modeling approach employed in this study can be extended to include real-time experimental data to propose new therapeutic interventions.

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Influence of environmental stress on immunity of swine

Medycyna Weterynaryjna ◽

10.21521/mw.5578 ◽

2016 ◽

Vol 72 (10) ◽

pp. 595-599

Author(s):

Zygmunt Pejsak ◽

Marian Truszczyński

Keyword(s):

Immune System ◽

Inflammatory Cytokines ◽

Immune Cells ◽

Management Practices ◽

Acute Phase Proteins ◽

Pathogenic Microorganisms ◽

Environmental Management Practices ◽

Chain Link ◽

Microbial Environment ◽

Pro Inflammatory Cytokines

This paper deals with pigs kept in environments, where they are exposed to a high number of pathogenic microbes and have reduced feed intake and growth, even when no obvious acute illness exists. According to the presented article this chronic drain on production is called immunologic stress. Sentinel immune cells (e.g. macrophages) supervise the diverse microbial environment by detecting pathogen – associated molecular patterns (PAMPs), which are molecules associated with groups of pathogens. The immune sentinels detect PAMPs mainly with Toll – like receptors (TLRs). Stimulation of macrophages through their TLRs leads to the synthesis and secretion of pro-inflammatory cytokines and prostaglandins, initiating the inflammatory response that recruits both immune molecules and circulating immune cells. Pro-inflammatory cytokines enable the immune system to communicate with other physiological systems. They rearrange the animal’s metabolic priorities, resulting in re-partitioning of nutrients away from productive processes towards responses that support the immune system. Thus, the immune system, through detection of PAMPs and production of pro-inflammatory cytokines, is the critical chain link connecting the pathogenic environment to productivity. The evaluation indicates, that at maintenance a healthy animal uses about 0,5-2% of the body’s lysine for leucocytes, antibodies and acute phase proteins. In the situation of contamination by pathogens of the environment the immune response is estimated to account for about 9% of the body’s lysine. Providing additional lysine in the diet does not improve the reduced growth of the pig, caused by immunologic stress as the result of contamination of the pig environment by pathogenic or facultatively pathogenic microorganisms. Thus, minimizing exposure to pathogenic microorganisms and providing sound environmental management practices is a high priority.

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