scholarly journals Enigma of IL-17 and Th17 Cells in Rheumatoid Arthritis and in Autoimmune Animal Models of Arthritis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Reka Kugyelka ◽  
Zoltan Kohl ◽  
Katalin Olasz ◽  
Katalin Mikecz ◽  
Tibor A. Rauch ◽  
...  

Rheumatoid arthritis (RA) is one of the most common autoimmune disorders characterized by the chronic and progressive inflammation of various organs, most notably the synovia of joints leading to joint destruction, a shorter life expectancy, and reduced quality of life. Although we have substantial information about the pathophysiology of the disease with various groups of immune cells and soluble mediators identified to participate in the pathogenesis, several aspects of the altered immune functions and regulation in RA remain controversial. Animal models are especially useful in such scenarios. Recently research focused on IL-17 and IL-17 producing cells in various inflammatory diseases such as in RA and in different rodent models of RA. These studies provided occasionally contradictory results with IL-17 being more prominent in some of the models than in others; the findings of such experimental setups were sometimes inconclusive compared to the human data. The aim of this review is to summarize briefly the recent advancements on the role of IL-17, particularly in the different rodent models of RA.

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 717
Author(s):  
Abhishek Kulkarni ◽  
Jerry L. Nadler ◽  
Raghavendra G. Mirmira ◽  
Isabel Casimiro

Lipoxygenases (LOXs) are lipid metabolizing enzymes that catalyze the di-oxygenation of polyunsaturated fatty acids to generate active eicosanoid products. 12-lipoxygenases (12-LOXs) primarily oxygenate the 12th carbon of its substrates. Many studies have demonstrated that 12-LOXs and their eicosanoid metabolite 12-hydroxyeicosatetraenoate (12-HETE), have significant pathological implications in inflammatory diseases. Increased level of 12-LOX activity promotes stress (both oxidative and endoplasmic reticulum)-mediated inflammation, leading to damage in these tissues. 12-LOXs are also associated with enhanced cellular migration of immune cells—a characteristic of several metabolic and autoimmune disorders. Genetic depletion or pharmacological inhibition of the enzyme in animal models of various diseases has shown to be protective against disease development and/or progression in animal models in the setting of diabetes, pulmonary, cardiovascular, and metabolic disease, suggesting a translational potential of targeting the enzyme for the treatment of several disorders. In this article, we review the role of 12-LOXs in the pathogenesis of several diseases in which chronic inflammation plays an underlying role.


2021 ◽  
Vol 14 (5) ◽  
pp. 483
Author(s):  
Tetsuya Kushikata ◽  
Kazuyoshi Hirota ◽  
Junichi Saito ◽  
Daiki Takekawa

Neuropeptide S (NPS) is an endogenous peptide that regulates various physiological functions, such as immune functions, anxiety-like behaviors, learning and memory, the sleep–wake rhythm, ingestion, energy balance, and drug addiction. These processes include the NPS receptor (NPSR1). The NPS–NPSR1 system is also significantly associated with the onset of disease, as well as these physiologic functions. For example, NPS is involved in bronchial asthma, anxiety and awakening disorders, and rheumatoid arthritis. In this review, among the various functions, we focus on the role of NPS in anesthesia-induced loss of consciousness; analgesia, mainly by anesthesia; and sleep–wakefulness. Progress in the field regarding the functions of endogenous peptides in the brain, including NPS, suggests that these three domains share common mechanisms. Further NPS research will help to elucidate in detail how these three domains interact with each other in their functions, and may contribute to improving the quality of medical care.


2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.

2005 ◽  
Vol 11 (5) ◽  
pp. 563-568 ◽  
Author(s):  
Ingmar Meinecke ◽  
Edita Rutkauskaite ◽  
Steffen Gay ◽  
Thomas Pap

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Se Eun Byeon ◽  
Young-Su Yi ◽  
Jueun Oh ◽  
Byong Chul Yoo ◽  
Sungyoul Hong ◽  
...  

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ning Qu ◽  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Jun-ichi Furusawa ◽  
Kotaro Kaneko ◽  
...  

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.


2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4968
Author(s):  
Samuel García-Arellano ◽  
Luis Alexis Hernández-Palma ◽  
Sergio Cerpa-Cruz ◽  
Gabriela Athziri Sánchez-Zuno ◽  
Melva Guadalupe Herrera-Godina ◽  
...  

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.


2021 ◽  
Vol 38 (3) ◽  
pp. 247-256
Author(s):  
Sonja Stojanović ◽  
Bojana Stamenković ◽  
Jovan Nedović ◽  
Ivana Aleksić ◽  
Jovana Cvetković

Nowadays, the appropriate control of rheumatoid arthritis (RA) involves the absence of clinical disease activity, delaying joint destruction as long as possible and adequate quality of life of the affected. With currently available therapeutic modalities, this therapeutic goal can be achieved in a large number of patients. The aim of this research was to determine the effectiveness of an IL-6 blocker (Tocilizumab) in patients with RA in everyday clinical practice. We also analyzed whether a change in the mode of drug administration (switching from intravenous to subcutaneous drug formulation) had an impact on drug effectiveness (using the DAS 28 SE and CDAI indexes) and quality of life of patients with RA (HAQ, Beck Depression Inventory, FACIT F score and SF 36 questionnaire). The study included 53 subjects diagnosed with RA, treated with Tocilizumab. After a six-month use of subcutaneous Tocilizumab, we concluded that the method of drug administration did not have an impact on its effectiveness and on all the examined parameters of quality of life assessment.


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