Role of reactive intermediates in the immunopathogenesis of the pristane-induced Balb/c model of lupus

Lupus ◽  
2011 ◽  
Vol 20 (13) ◽  
pp. 1421-1425 ◽  
Author(s):  
U Minhas ◽  
P Das ◽  
A Bhatnagar
Keyword(s):  
Lupus Erythematosus ◽  
Immune Reaction ◽  
Reactive Intermediates ◽  
Peritoneal Macrophages ◽  
Innate Immune ◽  
Antioxidant Defences ◽  
Single Intraperitoneal Injection ◽  
New Findings ◽  
Autoimmune Condition

Pristane-induced lupus in Balb/c mice represents an environmentally induced lupus model which is widely used for unravelling the mystery of the pathogenesis of the disease. An intraperitoneal innate immune reaction to pristane is primarily accountable for the development of the systemic lupus erythematosus-like disease in the model. In this study, reactive oxygen species (ROS) and nitric oxide (NO) levels were assessed (as a measure of chronic inflammation) in the peritoneum of the Balb/c model of SLE-like disease 6 months after a single intraperitoneal injection of pristane. Levels of ROS in peritoneal macrophages were significantly enhanced (mean fluorescence value ± SD: 648 ± 100.9) in pristane-treated mice (PT) as compared with control mice (mean fluorescence value ± SD: 79 ± 7.8) treated with phosphate buffer saline (PBST). An immunofluorescence study reveal the localization of ROS within nuclei, suggesting oxidative damage. Similarly, levels of NO were also markedly raised in PT mice (34.71 µmol/l ± 8.48) as compared with PBST mice (1.36 nmol/l ± 0.14). These new findings lead to speculation about the role of reactive intermediates in the development of disease. This study proposes that the sustained production of reactive intermediates during chronic intraperitoneal inflammation might reduce antioxidant defences and lead to a condition of oxidative stress, which might further be responsible for this autoimmune condition.

Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated?

2020 ◽  
Author(s):  
Rodolfo Perez-Alamino ◽  
Raquel Cuchacovich ◽  
Luis R. Espinoza ◽  
Constance P. Porretta ◽  
Arnold H. Zea
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Cells ◽  
Systemic Lupus

scholarly journals Stem Cell Therapy and Regenerative Medicine in Autoimmune Diseases

2021 ◽  
Author(s):  
Bhuvaneshwari Sampath ◽  
Priyadarshan Kathirvelu ◽  
Kavitha Sankaranarayanan
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Regenerative Medicine ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoimmune Condition ◽  
Recent Trends

The role of immune system in our body is to defense against the foreign bodies. However, if the immune system fails to recognize self and non-self-cells in our body leads to autoimmune diseases. Widespread autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, and more yet to be added to the list. This chapter discusses about how stem cell-based therapies and advancement of regenerative medicine endow with novel treatment for autoimmune diseases. Furthermore, in detail, specific types of stem cells and their therapeutic approach for each autoimmune condition along with their efficiency to obtain desired results are discussed. Ultimately, this chapter describes the recent trends in treating autoimmune diseases effectively using advanced stem cell research.

The innate immune system in human systemic lupus erythematosus

2017 ◽  
Vol 131 (8) ◽  
pp. 625-634 ◽  
Author(s):  
Marc Weidenbusch ◽  
Onkar P. Kulkarni ◽  
Hans-Joachim Anders
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Innate Immune System ◽  
Innate Immune ◽  
Type I ◽  
Human Systemic Lupus Erythematosus ◽  
Systemic Lupus ◽  
Adaptive Immune

Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease. This is why targeting the innate immune system offers an additional means of treating SLE. First trials assessing the efficacy of anti-type I interferon (IFN) therapy or modulators of pattern recognition receptor (PRR) signalling have been attempted. In this review, we summarize the available evidence on the role of several distinct innate immune elements, especially neutrophils and dendritic cells as well as the IFN system, as well as specific innate PRRs along with their signalling pathways. Finally, we highlight recent clinical trials in SLE addressing one or more of the aforementioned components of the innate immune system.

scholarly journals Neutrophil in Reverse Migration: Role in Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing Ji ◽  
Jie Fan
Keyword(s):  
Host Response ◽  
Immune Reaction ◽  
Innate Immune ◽  
Polymorphonuclear Neutrophils ◽  
Current Evidence ◽  
Protective Response ◽  
Reverse Migration ◽  
Inflammatory Site ◽  
Life Threatening

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. During the development and progression of sepsis, polymorphonuclear neutrophils (PMNs) are the most abundantly recruited innate immune cells at sites of infection, playing critical roles in the elimination of local infection and healing of the injury. PMN reverse migration (rM) describes the phenomenon in which PMNs migrate away from the inflammatory site back into the vasculature following the initial PMN infiltration. The functional role of PMN rM within inflammatory scenarios requires further exploration. Current evidence suggests that depending on the context, PMN rM can be both a protective response, by facilitating an efficient resolution to innate immune reaction, and also a tissue-damaging event. In this review, we provide an overview of current advancements in understanding the mechanism and roles of PMN rM in inflammation and sepsis. A comprehensive understanding of PMN rM may allow for the development of novel prophylactic and therapeutic strategies for sepsis.

scholarly journals The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Lixiang Sun ◽  
Wenjie Liu ◽  
Ling-juan Zhang
Keyword(s):  
Atopic Dermatitis ◽  
Human Body ◽  
Lupus Erythematosus ◽  
Mammalian Cells ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Host Responses ◽  
Molecular Patterns

As the key defense molecules originally identified in Drosophila, Toll-like receptor (TLR) superfamily members play a fundamental role in detecting invading pathogens or damage and initiating the innate immune system of mammalian cells. The skin, the largest organ of the human body, protects the human body by providing a critical physical and immunological active multilayered barrier against invading pathogens and environmental factors. At the first line of defense, the skin is constantly exposed to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and TLRs, expressed in a cell type-specific manner by various skin cells, serve as key molecules to recognize PAMPs and DAMPs and to initiate downstream innate immune host responses. While TLR-initiated inflammatory responses are necessary for pathogen clearance and tissue repair, aberrant activation of TLRs will exaggerate T cell-mediated autoimmune activation, leading to unwanted inflammation, and the development of several skin diseases, including psoriasis, atopic dermatitis, systemic lupus erythematosus, diabetic foot ulcers, fibrotic skin diseases, and skin cancers. Together, TLRs are at the interface between innate immunity and adaptive immunity. In this review, we will describe current understanding of the role of TLRs in skin defense and in the pathogenesis of psoriasis and atopic dermatitis, and we will also discuss the development and therapeutic effect of TLR-targeted therapies.

scholarly journals Jieduquyuziyin Prescription-Treated Rat Serum Suppresses Activation of Peritoneal Macrophages in MRL/Lpr Lupus Mice by Inhibiting IRAK1 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Lina Ji ◽  
Xiaoli Hou ◽  
Xian Deng ◽  
Xuemin Fan ◽  
Aiwen Zhuang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Peritoneal Macrophages ◽  
Rat Serum ◽  
Western Blot Method ◽  
Jieduquyuziyin Prescription ◽  
Chronic Autoimmune Disease ◽  
Cell Supernatant

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and Jieduquyuziyin prescription (JP) is a traditional Chinese medicine (TCM) formula that has been testified to be effective for SLE treatment as an approved hospital prescription for many years in China. However, its mechanism of action in the treatment of this disease is largely unknown. The purpose of this study was to determine whether JP-treated rat serum can inhibit the activation of peritoneal macrophages in MRL/lpr mice by downregulating the IRAK1 signaling pathway, thereby achieving the effect of improving SLE. The JP-treated rat serum was prepared, and the peritoneal macrophages of MRL/lpr lupus mice were isolated in vitro, and the effect of JP on cell viability was detected by the CCK8 method. After LPS induction and shRNA lentiviral transfection, the effect of JP on the expression of IRAK1 in cells was detected by immunofluorescence staining. The content of TNF-α and IL-6 in the cell supernatant was determined by ELISA. The expression of IRAK1, NF-κB, TNF-α, and IL-6 mRNA was detected by RT-PCR, and the expression levels of IRAK1, p-IRAK1, TRAF6, IKBα, p-IKBα, IKK + IKK, NF-κB, and p-NF-κB proteins was detected by western blot method. We investigated the role of JP in peritoneal macrophages of the MRL/lpr mouse and identified the possible mechanisms of action. The results showed that JP could reduce the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of inflammatory cytokines, including TNF-α and IL-6. In addition, after the transfection of cells with shRNA lentiviral, the results of JP tended to be consistent. In conclusion, JP may inhibit the activation of peritoneal macrophages in MRL/lpr mice by downregulating the IRAK1-NF-κB signaling pathway, and IRAK1 may be a potential target for JP treatment of SLE.

Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated?

2021 ◽  
Vol 17 (4) ◽  
pp. 187-191
Author(s):  
Rodolfo Perez-Alamino ◽  
Raquel Cuchacovich ◽  
Luis R. Espinoza ◽  
Constance P. Porretta ◽  
Arnold H. Zea
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Cells ◽  
Systemic Lupus

scholarly journals Intestinal macrophages in mucosal immunity and their role in systemic lupus erythematosus disease

Lupus ◽  
2018 ◽  
Vol 27 (12) ◽  
pp. 1898-1902 ◽  
Author(s):  
F Pan ◽  
W Tang ◽  
Z Zhou ◽  
G Gilkeson ◽  
R Lang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Responses ◽  
Lupus Erythematosus ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Systemic Lupus ◽  
Innate Immune Signaling ◽  
Immune Signaling Pathway

Monocytes play an important role in inducing host systemic immunity against invading pathogens and inflammatory responses. After activation, monocytes migrate to tissue sites, where they initiate both innate and adaptive immune responses, and become macrophages. Although mucosal macrophages produce inflammatory cytokines in response to pathogens, the perturbations in innate immune signaling pathway have been implicated in autoimmune diseases such as systemic lupus erythematosus (SLE). In this review, we focus on the role of human macrophages in intestinal innate immune responses, homeostasis, and SLE disease. We further discuss sex differences in the intestinal macrophages and their role in the physiology and pathogenesis of SLE.

scholarly journals Inflammasomes in pancreatic physiology and disease

2015 ◽  
Vol 308 (8) ◽  
pp. G643-G651 ◽  
Author(s):  
Rafaz Hoque ◽  
Wajahat Z. Mehal
Keyword(s):  
Metabolic Regulation ◽  
Recent Progress ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Cell Specificity ◽  
Immune Mediated ◽  
New Findings ◽  
Inflammasome Component

In this review we summarize the role of inflammasomes in pancreatic physiology and disease with a focus on acute pancreatitis where much recent progress has been made. New findings have identified inducers of and cell specificity of inflammasome component expression in the pancreas, the contribution of inflammasome-regulated effectors to pancreatitis, and metabolic regulation of inflammasome activation, which are strong determinants of injury in pancreatitis. New areas of pancreatic biology will be highlighted in the context of our evolving understanding of gut microbiome- and injury-induced inflammasome priming, pyroptosis, and innate immune-mediated regulation of cell metabolism.

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