scholarly journals Cancer Morbidity in Rheumatoid Arthritis: Role of Estrogen Metabolites

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Wahid Ali Khan ◽  
Mohd Wajid Ali Khan
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Free Radicals ◽  
Cancer Risk ◽  
Immune Responses ◽  
Redox Cycle ◽  
Estrogen Metabolites ◽  
Dna Modifications ◽  
Cancer Morbidity

Estrogen metabolites have been implicated in rheumatoid arthritis (RA) and cancer, although the mechanism remains unestablished. Some estrogen metabolites, which are used for the assessment of cancer risk, play an important role in RA. The pathways by which malignancies associated with RA remain elusive. Possible mechanism involves enzymatic or nonenzymatic oxidation of estrogen into catecholestrogen metabolites through semiquinone and quinone redox cycle to produce free radicals that can cause DNA modifications. Modifications of DNA alter its immunogenicity and trigger various immune responses leading to elevated levels of cancer and RA antibodies. However, the role of different estrogen metabolites as a mediator of immune response cannot be ruled out in various immune-related diseases.

scholarly journals The Role of Src Kinase in Macrophage-Mediated Inflammatory Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Se Eun Byeon ◽  
Young-Su Yi ◽  
Jueun Oh ◽  
Byong Chul Yoo ◽  
Sungyoul Hong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Src Kinase ◽  
Multiple Roles ◽  
Cellular Migration ◽  
Pharmaceutical Drugs ◽  
Tyrosine Protein Kinase

Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases.

scholarly journals Haptoglobin and Its Related Protein, Zonulin—What Is Their Role in Spondyloarthropathy?

2021 ◽  
Vol 10 (5) ◽  
pp. 1131
Author(s):  
Magdalena Chmielińska ◽  
Marzena Olesińska ◽  
Katarzyna Romanowska-Próchnicka ◽  
Dariusz Szukiewicz
Keyword(s):  
Immune Response ◽  
Free Radicals ◽  
Immune System ◽  
Potential Role ◽  
Acute Phase Protein ◽  
Related Protein ◽  
Functional Differences ◽  
Phase Protein ◽  
Its Polymorphism

Haptoglobin (Hp) is an acute phase protein which supports the immune response and protects tissues from free radicals. Its concentration correlates with disease activity in spondyloarthropathies (SpAs). The Hp polymorphism determines the functional differences between Hp1 and Hp2 protein products. The role of the Hp polymorphism has been demonstrated in many diseases. In particular, the Hp 2-2 phenotype has been associated with the unfavorable course of some inflammatory and autoimmune disorders. Its potential role in modulating the immune system in SpA is still unknown. This article contains pathophysiological considerations on the potential relationship between Hp, its polymorphism and SpA.

scholarly journals Role of Microbiome in Rheumatic Diseases

2017 ◽  
Vol 17 (2) ◽  
pp. 58-63 ◽  
Author(s):  
Chi Kit Au ◽  
Tin Lok Lai ◽  
Cheuk Wan Yim
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Rheumatic Diseases ◽  
Pivotal Role ◽  
Human Gut ◽  
Future Role ◽  
Human Gut Microbiota ◽  
Rheumatic Manifestations

AbstractMajority of rheumatic diseases are complex and multifactorial in etiology. Emerging studies has suggested that the change of human microbiota, especially in the gut, play a pivotal role in its pathogenesis. Dysequilibrium of the gut microbiota triggers the imbalance between pro- and anti- inflammatory immune responses and results in different rheumatic manifestations, such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). In this article, current and future role of the human gut microbiota in rheumatic diseases are discussed.

scholarly journals Prostaglandins and Rheumatoid Arthritis

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mohammad Javad Fattahi ◽  
Abbas Mirshafiey
Keyword(s):  
Rheumatoid Arthritis ◽  
Arachidonic Acid ◽  
Immune Responses ◽  
Cartilage Destruction ◽  
Heterogeneous Population ◽  
Therapeutic Protocol ◽  
Site Of Action ◽  
And Cartilage ◽  
Homeostatic Mechanisms

Rheumatoid arthritis (RA) is a chronic, autoimmune, and complex inflammatory disease leading to bone and cartilage destruction, whose cause remains obscure. Accumulation of genetic susceptibility, environmental factors, and dysregulated immune responses are necessary for mounting this self-reacting disease. Inflamed joints are infiltrated by a heterogeneous population of cellular and soluble mediators of the immune system, such as T cells, B cells, macrophages, cytokines, and prostaglandins (PGs). Prostaglandins are lipid inflammatory mediators derived from the arachidonic acid by multienzymatic reactions. They both sustain homeostatic mechanisms and mediate pathogenic processes, including the inflammatory reaction. They play both beneficial and harmful roles during inflammation, according to their site of action and the etiology of the inflammatory response. With respect to the role of PGs in inflammation, they can be effective mediators in the pathophysiology of RA. Thus the use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in RA. In this paper, we try to elucidate the role of PGs in the immunopathology of RA.

scholarly journals Dual Role of Toll-Like Receptor 7 in the Pathogenesis of Rabies Virus in a Mouse Model

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Zhaochen Luo ◽  
Lei Lv ◽  
Yingying Li ◽  
Baokun Sui ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Immune Responses ◽  
Rabies Virus ◽  
Mouse Brain ◽  
Early Stage ◽  
Toll Like Receptor ◽  
Innate Recognition ◽  
Recognition Receptor

ABSTRACT Rabies, caused by rabies virus (RABV), is a fatal encephalitis in humans and other mammals, which continues to present a public health threat in most parts of the world. Our previous study demonstrated that Toll-like receptor 7 (TLR7) is essential in the induction of anti-RABV antibodies via the facilitation of germinal center formation. In the present study, we investigated the role of TLR7 in the pathogenicity of RABV in a mouse model. Using isolated plasmacytoid dendritic cells (pDCs), we demonstrated that TLR7 is an innate recognition receptor for RABV. When RABV invaded from the periphery, TLR7 detected viral single-stranded RNA and triggered immune responses that limited the virus’s entry into the central nervous system (CNS). When RABV had invaded the CNS, its detection by TLR7 led to the production of cytokines and chemokines and an increase the permeability of the blood-brain barrier. Consequently, peripheral immune cells, including pDCs, macrophages, neutrophils, and B cells infiltrated the CNS. While this immune response, triggered by TLR7, helped to clear viruses, it also increased neuroinflammation and caused immunopathology in the mouse brain. Our results demonstrate that TLR7 is an innate recognition receptor for RABV, which restricts RABV invasion into the CNS in the early stage of viral infection but also contributes to immunopathology by inducing neuroinflammation. IMPORTANCE Developing targeted treatment for RABV requires understanding the innate immune response to the virus because early virus clearance is essential for preventing the fatality when the infection has progressed to the CNS. Previous studies have revealed that TLR7 is involved in the immune response to RABV. Here, we establish that TLR7 recognizes RABV and facilitates the production of some interferon-stimulated genes. We also demonstrated that when RABV invades into the CNS, TLR7 enhances the production of inflammatory cytokines which contribute to immunopathology in the mouse brain. Taken together, our findings suggest that treatments for RABV must consider the balance between the beneficial and harmful effects of TLR7-triggered immune responses.

scholarly journals Crosstalk between Dendritic Cells and Immune Modulatory Agents against Sepsis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 323 ◽  
Author(s):  
Guoying Wang ◽  
Xianghui Li ◽  
Lei Zhang ◽  
Abualgasim Elgaili Abdalla ◽  
Tieshan Teng ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Th2 Responses ◽  
Novel Strategy

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.

The rôle of cortisol and β-endorphin in the response of the immune system to weaning in lambs

1998 ◽  
Vol 66 (2) ◽  
pp. 397-402 ◽  
Author(s):  
S. M. Rhind ◽  
H. W. Reid ◽  
S. R. McMillen ◽  
G. Palmarini
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Stress Hormone ◽  
Keyhole Limpet Haemocyanin ◽  
Weaning Stress ◽  
Cell Mediated Immune Response ◽  
Acth Treatment ◽  
Induced Changes ◽  
The Relationship

AbstractThe relationship between weaning stress-induced changes in stress hormone profiles and immune function was investigated in groups of 10 lambs immunized against adrenocorticotrophic hormone (ACTH; treatment A) or fi-endorphin (treatment B) to reduce the circulating concentrations of cortisol and fi-endorphin respectively. Control animals (treatment C) were immunized against a porcine thyroglobulin carrier protein. Application of weaning stress was associated with significantly elevated plasma cortisol concentrations but no significant increase in fi-endorphin concentrations in C lambs. Immunization against ACTH suppressed the post-weaning increase in cortisol concentration. This was associated with a transient reduction in the lymphocyte stimulation response to keyhole limpet haemocyanin (KLH) antigen in the A animals but there was no effect on the antibody response or interferon-y production by antigen stimulated lymphocytes. There were no significant effects of immunization against fi-endorphin on the capacity to mount antibody or cell-mediated immune responses. It is concluded that weaning stress-induced increases in cortisol did not inhibit the immune response. Since cortisol concentrations and the cell mediated immune response at 8 days after immunization were positively associated it is concluded that these indices are not independent measures of stress.

The role of cytokines in immunological tolerance: potential for therapy

2000 ◽  
Vol 2 (9) ◽  
pp. 1-20 ◽  
Author(s):  
Mark Harber ◽  
Anette Sundstedt ◽  
David Wraith
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Animal Models ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immunological Tolerance ◽  
Immunomodulatory Effects ◽  
Clinical Potential

Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

scholarly journals Innate Immune Responses of Bat and Human Cells to Filoviruses: Commonalities and Distinctions

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Ivan V. Kuzmin ◽  
Toni M. Schwarz ◽  
Philipp A. Ilinykh ◽  
Ingo Jordan ◽  
Thomas G. Ksiazek ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Antiviral Effect ◽  
Human Cells ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Symptomatic Disease ◽  
Ifn Γ

ABSTRACT Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (Rousettus aegyptiacus); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells. The study demonstrated that EBOV and MARV replicate to similar levels in all tested cell lines, indicating that permissiveness for EBOV at cell and organism levels do not necessarily correlate. Filoviruses, particularly MARV, induced a potent innate immune response in rousette cells, which was generally stronger than that in human cells. Both EBOV VP35 and VP24 IID were found to suppress the innate immune response in rousette cells, but only VP35 IID appeared to promote virus replication. Along with IFN-α and IFN-β, IFN-γ was demonstrated to control filovirus infection in bat cells but not in human cells, suggesting host species specificity of the antiviral effect. The antiviral effects of bat IFNs appeared not to correlate with induction of IFN-stimulated genes 54 and 56, which were detected in human cells ectopically expressing bat IFN-α and IFN-β. As bat IFN-γ induced the type I IFN pathway, its antiviral effect is likely to be partially induced via cross talk. IMPORTANCE Bats serve as reservoirs for multiple emerging viruses, including filoviruses, henipaviruses, lyssaviruses, and zoonotic coronaviruses. Although there is no evidence for symptomatic disease caused by either Marburg or Ebola viruses in bats, spillover of these viruses into human populations causes deadly outbreaks. The reason for the lack of symptomatic disease in bats infected with filoviruses remains unknown. The outcome of a virus-host interaction depends on the ability of the host immune system to suppress viral replication and the ability of a virus to counteract the host defenses. Our study is a comparative analysis of the host innate immune response to either MARV or EBOV infection in bat and human cells and the role of viral interferon-inhibiting domains in the host innate immune responses. The data are useful for understanding the interactions of filoviruses with natural and accidental hosts and for identification of factors that influence filovirus evolution.

scholarly journals Chlamydial abortion of ewes and goats. I. Current aspects on etiology, pathogenesis, immune mechanisms and epizootiology of disease

2018 ◽  
Vol 53 (1) ◽  
pp. 9
Author(s):  
V. SIARKOU (Β. ΣΙΑΡΚΟΥ)
Keyword(s):  
Experimental Data ◽  
Immune Response ◽  
New Species ◽  
Immune Responses ◽  
Disease Transmission ◽  
Latent Infection ◽  
Recent Experimental Data ◽  
New Genera ◽  
Ifn Γ

Chlamydial abortion constitutes one of the major causes of infectious abortion in sheep and goats. The disease leads to considerable losses in most sheep and goat-rearing countries, as well as, in Greece. In this paper, a review of the causative agent, pathogenesis, host immune response and epizootiology is presented. After recent changes, that have occured in the taxonomy of chlamydiae, it is necessary to refer to new families, new genera and new species within the order Chlamydiales, with emphasis on new species of Chlamydophila abortus, the causal agent of chlamydial abortion. This study reviews the recent experimental data which indicate the sites of entry of the organism, the way of its dissemination and establishment to the placenta. It also reviews current research on the humoral and cell-mediated immune responses, the role of the IFN-γ in latent infection and this of Tcells in the protective immune response. Finally, particular reference is given on the role of the male in the disease transmission and the role of inter-species contamination in chlamydial abortion.

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