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[The immunomodulatory role of sodium].
Agócs, RI, Sugár, D, Pap, D, Szabó, AJ
Orvosi hetilap. 2019;(17):646-653
Abstract
High salt intake, which is common in the Western world, is the cause of several lifestyle diseases. Recent investigations shed light on novel extrarenal processes, which play role in the maintenance of sodium balance. In the short term, sodium storage of the skin may serve as a buffer against volume overload arising from the osmotic properties of sodium. Increased tissue sodium concentration may also potentiate immune response against infections. In the long run, however, tissue sodium concentration over a certain limit may initiate pathophysiological processes by provoking inflammatory response. Due to the immune modulating role of sodium, the effector cells of the innate as well as the adaptive immune system are activated, while certain regulator cells of the same systems are repressed, ultimately resulting in a proinflammatory state characterized by the imbalance of the immune system. Experiments applying dietary salt overload/salt depletion imply the role of sodium in the initiation/exacerbation of several diseases. Thus the relationship between sodium and the immune system may give an explanation to the pathomechanism of diseases with so far unknown origin such as hypertonia (primary, salt sensitive) or autoimmune diseases - all these putting tremendous pressure on the healthcare system due to their increasing incidence. Orv Hetil. 2019; 160(17): 646-653.
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Immunologic cellular characteristics of the tumour microenvironment of hepatocellular carcinoma drive patient outcomes.
Atanasov, G, Dino, K, Schierle, K, Dietel, C, Aust, G, Pratschke, J, Seehofer, D, Schmelzle, M, Hau, HM
World journal of surgical oncology. 2019;(1):97
Abstract
BACKGROUND Anti-tumour immune competence has an impact in hepatocarcinogenesis and success of anti-cancer therapies. Tumour-infiltrating lymphocytes (TILs) and monocytes/macrophages (TAMs) are proposed to have significance in cancer. However, there is only limited data concerning their impact on patient outcome and survival in hepatocellular carcinoma (HCC). METHODS Frequencies of CD68+, CD163+ M2-polarized TAMs and TILs were measured in de novo HCC tumours in non-cirrhosis (n = 58) using immunohistology and correlated to patients' clinicopathological characteristics and survival rates. RESULTS Patients with tumours marked by appearance of TILs and CD68+ TAMs showed an improved 1-, 3- and 5-year recurrence-free survival (all p ≤ 0.05). CD68+ TAMs were associated with reduced incidence of recurrent and multifocal disease. Conversely, CD163+ TAMs were associated with multifocal HCC and lymphangiosis carcinomatosa (all p ≤ 0.05). CONCLUSIONS TILs and CD68+ TAMs are associated with multiple tumour characteristics and patient survival in HCC. However, there is only scarce data about the biology underlying their mechanistic involvement in human tumour progression. Thus, experimental data on functional links might help develop novel immunologic checkpoint inhibitor targets for liver cancer.
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3.
NLRP3 inflammasome: Its regulation and involvement in atherosclerosis.
Hoseini, Z, Sepahvand, F, Rashidi, B, Sahebkar, A, Masoudifar, A, Mirzaei, H
Journal of cellular physiology. 2018;(3):2116-2132
Abstract
Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL-1β and proIL-18 to mature forms and initiate pyroptosis via cleaving procaspase-1. The most well-known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL-1β, IL-18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid-based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low-density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome. In addition, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and lysosome rupture, which are implicated in inflammasome activation, have been discussed as important events in atherosclerosis. In spite of these clues, some studies have reported that NLRP3 inflammasome has no significant effect in atherogenesis. Our review reveals that some molecules such as JNK-1 and ASK-1 (upstream regulators of inflammasome activation) can reduce atherosclerosis through inducing apoptosis in macrophages. Notably, NLRP3 inflammasome can also cause apoptosis in macrophages, suggesting that NLRP3 inflammasome may mediate JNK-induced apoptosis, and the apoptotic function of NLRP3 inflammasome may be a reason for the conflicting results reported. The present review shows that the role of NLRP3 in atherogenesis can be significant. Here, the molecular pathways of NLRP3 inflammasome activation and the implications of this activation in atherosclerosis are explained.
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Emerging Role of IL-4-Induced Gene 1 as a Prognostic Biomarker Affecting the Local T-Cell Response in Human Cutaneous Melanoma.
Ramspott, JP, Bekkat, F, Bod, L, Favier, M, Terris, B, Salomon, A, Djerroudi, L, Zaenker, KS, Richard, Y, Molinier-Frenkel, V, et al
The Journal of investigative dermatology. 2018;(12):2625-2634
Abstract
Several studies have emphasized the importance of immune composition of the melanoma microenvironment for clinical outcome. The contribution of IL4I1, a phenylalanine oxidase with immunoregulatory functions, has not been yet explored. Here we studied a primary cutaneous melanoma series from stage I-III patients to investigate the association between in situ IL4I1 expression and clinical parameters or tumor-infiltrating T-cell subsets. IL4I1 was detected in 87% of tumors and was mainly expressed by tumor-associated macrophages and very rare FoxP3+ regulatory T cells. The proportion of IL4I1+ cells was higher in patients with an ulcerated melanoma or with a positive sentinel lymph node and tended to correlate with a rapid relapse and shorter overall survival. This proportion also correlated positively with the presence of regulatory T cells and negatively with the presence of cytotoxic CD8+ T cells. The location of IL4I1+ cells may also be relevant to predict prognosis, because their presence near tumor cells was associated with sentinel lymph node invasion and higher melanoma stage. Collectively, our data show that IL4I1+ cells shape the T-cell compartment and are associated with a higher risk of poor outcome in melanoma, supporting a key role for IL4I1 in immune evasion.
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Transfusion-related immunomodulation: a reappraisal.
Youssef, LA, Spitalnik, SL
Current opinion in hematology. 2017;(6):551-557
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Abstract
PURPOSE OF REVIEW This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing 'pure' red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the 'storage lesion.' Macrophages are a key cell type involved in physiological and pathological RBC clearance and iron recycling. The plasticity and diversity of macrophages makes these cells potential mediators of immune suppression that could constitute TRIM. RECENT FINDINGS Recent reports identified the capacity of macrophages and monocytes to exhibit 'memory.' Exposure to various stimuli, such as engulfment of apoptotic cells and interactions with ß-glucan and lipopolysaccharide, were found to induce epigenetic, metabolic, and functional changes in certain myeloid cells, particularly macrophages and monocytes. SUMMARY Macrophages may mediate the immunosuppressive aspects of TRIM that arise as a result of transfused RBCs and their storage lesion induced by-products.
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Macrophage Targeted Cellular Carriers for Effective Delivery of Anti-Tubercular Drugs.
Agnihotri, J, Singh, S, Wais, M, Pathak, A
Recent patents on anti-infective drug discovery. 2017;(2):162-183
Abstract
BACKGROUND Newly developed vaccine VPM1002 confers paradigm swing in the prophylactic treatment of tuberculosis (TB). Multi-drug resistant and latent TB in adults as well as in underprivileged patients is instigating menace over world population if the host is immune-compromised. METHODS One third of the world's population is infected with TB. Recently it is estimated around 9.6 million people around the world became sick with TB disease. There were 1.5 million TB-related deaths worldwide. Therefore with the advent in biotechnology and Nano engineering, newly adapted survival molecular mechanism of Mycobacterium tuberculosis, new targets receptors on alveolar macrophages must be explored out for eradication of TB from the globe. Macrophage acts as a reservoir of phagocytic receptors to execute diverse physiological functions as well as to perform defense mechanism. RESULTS Advances in novel carriers open new era for the treatment of tuberculosis which remains a very substantial global health encumbrance. Different binding receptors especially mannose, folate and scavenger receptors are attractive platform for internalization of therapeutics in alveolar macrophage. Nano-carriers and nano-devices designed after the acquaintance of receptor composition and functioning affords site specific targeting of biodegradable and biocompatible drug delivery systems for the treatment of tuberculosis offering complete cure and patient compliance. CONCLUSION This chapter encompasses recent studies on nanocarriers and new treatment strategies for tuberculosis. In spite of the budding benefits of nano carriers, many limitations still remain to be overcome such as poor oral stability, instability in circulation, inadequate tissue distribution as well as toxicity to normal cells.