• Biomolecules & Therapeutics
• /
• 제23권1호
• /
• pp.71-76
• /
• 2015

Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed $PPAR{\gamma}$-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a $PPAR{\gamma}$ ligand, reduced both IL-$1{\beta}$-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-$1{\beta}$. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical $PPAR{\gamma}$ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.

• Molecules and Cells
• /
• 제44권5호
• /
• pp.301-309
• /
• 2021

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. ILCs can be categorized into three groups on the basis of the transcription factors that direct their functions and the cytokines they produce. Notably, these functions parallel the effector functions of T lymphocytes. ILCs play a frontline role in host defense and tissue homeostasis by responding rapidly to environmental factors, conducting effector responses in a tissue-specific manner, and interacting with hematopoietic and non-hematopoietic cells throughout the body. Moreover, recent studies reveal that ILCs are involved in development of various inflammatory diseases, such as respiratory diseases, autoimmune diseases, or cancer. In this review, we discuss the recent findings regarding the biology of ILCs in health and inflammatory diseases.

• 통합자연과학논문집
• /
• 제8권3호
• /
• pp.164-175
• /
• 2015

CXCR3 is a C-X-C chemokine receptor type 3 also known as GPR9 and CD183. CXCR3 is a G-Protein coupled chemokine receptor which interacts with three endogenous interferon inducible chemokine's (CXCL9, CXCL10 and CXCL11) and is proved to play a vital role in the Th1 inflammatory responses. CXCR3 has been implicated to be associated with various disease conditions like inflammatory diseases, autoimmune diseases, type I diabetes and acute cardiac allograft rejection. Therefore CXCR3 receptor is found to be an attractive therapeutic target for the treatment of inflammatory diseases. Inorder to decipher the biological function of a CXCR3, 3D structure is of much important but the crystal structure for CXCR3 has not yet been resolved. Hence, in the current study Homology modeling of CXCR3 was performed against various templates and validated using different parameters to suggest the best model for CXCR3. The reported best model can be used for further studies such as docking to identify the important binding site residues.

• 동의생리병리학회지
• /
• 제19권4호
• /
• pp.934-937
• /
• 2005

Inflammatory cytokine, abundantly produced in Hashimoto's thyroiditis, induced Fas expression in normal thyrocytes. We determined that susceptibility to Fas-activated apoptosis could be influenced by inflammatory cytokine and investigated a potential role of Gamgung-tang (GGT, Glycyrrhizae Radix, black beans, Angelicae Radix and Cnidii Rhizoma) in the thyroid follicular cells. $IL-1\beta$ was able to induce Fas expression in normal thyrocytes. GGT inhibited $IL-1\beta-induced$ Fas expression. Thyroid follicular cells were found to undergo DNA fragmentation with the inflammatory cytokines. GGT inhibited DNA fragmentation in a dose-dependent manner. These results suggest that GGT inhibit Fas-mediated apoptosis in thyroid follicular cells, therefore, may have therapeutic potential in the treatment of autoimmune chronic thyroiditis.

• Childhood Kidney Diseases
• /
• 제28권1호
• /
• pp.44-50
• /
• 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that affects multiple organs. More than half of the patients with SLE have kidney involvement, and up to 10% of patients with lupus nephritis develop end-stage renal disease (ESRD). Central nervous system (CNS) involvement in SLE occurs in 21% to 95% of patients. Severe neurological manifestations such as seizures, cerebrovascular disease, meningitis, and cerebrovascular accidents can develop in childhood-onset SLE, but cerebral infections, such as brain abscess and hemorrhage, are seldom reported in lupus nephritis, even in adults. Here, we report a rare case of childhood-onset SLE with ESRD, cerebral abscess, and hemorrhage. A 9-year-old girl diagnosed with lupus nephritis was administered high-dose steroids and immunosuppressant therapy to treat acute kidney injury (AKI) and massive proteinuria. The AKI deteriorated, and after 3 months, she developed ESRD. She received hemodialysis three times a week along with daily peritoneal dialysis to control edema. She developed seizures, and imaging showed a brain abscess. This was complicated by spontaneous cerebral hemorrhage, and she became unstable. She died shortly after the hemorrhage was discovered. In conclusion, CNS complications should always be considered in clinical practice because they increase mortality, especially in those with risk factors for infection.

• IMMUNE NETWORK
• /
• 제13권6호
• /
• pp.257-263
• /
• 2013

Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-${\gamma}$, and IL-6 and increased level of immunoregulatory IL-10.

• IMMUNE NETWORK
• /
• 제24권1호
• /
• pp.10.1-10.17
• /
• 2024

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

• 셀메드
• /
• 제11권1호
• /
• pp.1.1-1.4
• /
• 2021

Background: Amavata is a disease that occurs as a result of the error of metabolism. Poor dietary habits and faulty Dincharya (daily regimen) and ritucharya (seasonal regimen) leading to deranged metabolism and Agni (metabolic fire) which results in the formation of Ama(undigested product of metabolism). When Amaconceals with Vata(subtle energy associated with movement) and circulates in the body under the influence of Vyana Vayu (omnipresent air)it clogs the srotasas (microchannels) and initiates the inflammatory cascade. Amavata is commonly correlated with rheumatoid arthritis (RA) while other forms of auto-immune disorders can also be included in Amavata.Dysbiosis of the gut microbiota (GM) has been connected to the onset of diverse autoimmune diseases. In this study, it was hypothesized that Panchakarma (bio-purificatory methods) based intervention such as Virechana Karma (therapeutic purgation) may influence microbiota. Materials and Methods: Various Ayurvedic literature were reviewed for the etiopathogenesis of Amavata. Different databases were searched with research papers related to Gut Dysbiosis and autoimmunity and management of RA. A connecting link between Intestinal Dysbiosis with the autoimmune mechanisms was established and it was also found that the bowel cleansing introduced a change to the GM. Conclusion: It was concluded that Virechana karma is effective in gut flora Dysbiosis. This study aims to correlate the ancient Ayurvedic principles related to Agni Bala(metabolic energy) and biopurificatory treatment modalities like Virechana karma (therapeutic purgation)with the modern concept of gut microbiota and its role in the pathogenesis of various autoimmune disorders such as rheumatoid arthritis. The article creates an understanding about principles of Ayurveda and its rationality in today's scientific world and thereby opens newer vistas of research in therapeutics from Ayurveda, which may be helpful in the management of various immune-mediated Diseases through Ayurveda.

• Molecules and Cells
• /
• 제42권12호
• /
• pp.906-918
• /
• 2019

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

• BMB Reports
• /
• 제53권2호
• /
• pp.65-73
• /
• 2020

Life expectancy has dramatically increased around the world over the last few decades, and staying healthier longer, without chronic disease, has become an important issue. Although understanding aging is a grand challenge, our understanding of the mechanisms underlying the degeneration of cell and tissue functions with age and its contribution to chronic disease has greatly advanced during the past decade. As our immune system alters with aging, abnormal activation of immune cells leads to imbalance of innate and adaptive immunity and develops a persistent and mild systemic inflammation, inflammaging. With their unique therapeutic properties, such as immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs) have been considered to be a promising source for treating autoimmune disease or as anti-aging therapy. Although direct evidence of the role of MSCs in inflammaging has not been thoroughly studied, features reported in senescent MSCs or the aging process of MSCs are associated with inflammaging; MSC niche-driven skewing of hematopoiesis toward the myeloid lineage or oncogenesis, production of pro-inflammatory cytokines, and weakening their modulative property on macrophage polarization, which plays a central role on inflammaging development. This review explores the role of senescent MSCs as an important regulator for onset and progression of inflammaging and as an effective target for anti-aging strategies.