Microglia-induced neurotoxicity occurs when inflammation mediated by microglia causes loss of neuronal structures or functions in the central nervous system implicated in stroke, spinal cord injury, sepsis, neurodegenerative diseases and even psychiatric illnesses. Various co-culture in vitro microglia-induced neurotoxicity (MINT) models have been established to enable an in-depth study of this process and yet there is a dearth of information regarding usages, advantages and limitations of each of the components of this model. In this review, we examined 56 MINTs for the cells, stimuli, parameters, methods of neurotoxicity measurement and formats of co-culture used in their construction. We aim to provide foundational information, overall guideline and framework for the novice researcher to develop his/her own model and for the advancement of improved, novel and more representative MINT models.
Introduction: Monocytes are essential phagocytic cells of the innate immune system as they are required for
the maintenance of tissue homeostasis. However, accumulation of monocytes is implicated in various chronic
inflammatory diseases like coronary heart disease, atherosclerosis and in autoimmune disorders. Therefore, the
number of monocytes must be carefully regulated to avoid monocyte induced inflammatory disorders. Mesenchymal
stem cells (MSCs) have shown to be effective against various inflammatory diseases due to their immunosuppressive
properties. The present study was designed to evaluate the less understood immunomodulatory effect of MSCs on
monocyte proliferation and survival. Method: Primary monocytes were isolated from peripheral human blood using
CD14+ monocyte isolation kit. The in house produced umbilical cord MSCs were co-cultured with monocytes
at different ratio and time; assessed for the monocyte viability, proliferation and cell cycle. Results: Mesenchymal
stem cells suppressed monocyte proliferation in a dose-dependent manner. The antiproliferative effect of MSCs was
mediated by cell cycle arrest, whereby monocytes were arrested in the G0/G1 phase of the cell cycle by preventing
them from progress into S and G2/M phases. Although cell cycle arrest could potentially lead to apoptosis; however,
MSCs significantly enhanced the monocytes survival and inhibited apoptosis. Conclusion: Human MSCs inhibit the
stimulated monocyte proliferation without inducing cellular apoptosis at in vitro. These results reveal that MSCs can
be utilised to control monocytes’ quantity during an unwanted immune response to maintain homeostasis.
Mesenchymal stem cells (MSCs) hold a great therapeutic potential for regenerative
medicine and tissue engineering due to inherent immunomodulatory and reparative properties. Hence,
it necessitates a readily available supplyof MSCs to meet the clinical demands adequately. Although,
a human placenta can produce MSCs, the in vitro culture-mediated cellular senescence often affect the
quality of cell product. Thus, the current study has explored the feasibility of basic fibroblast growth
factor (bFGF) to enhance the growth of placenta-derived MSCs (PLC-MSCs). Methods:The basic
fibroblast growth factor (bFGF) was supplemented to optimise the growth of MSCs. The effects of
bFGF on morphology, growth kinetics and cytokine secretion of PLC-MSCs were assessed. Results:
The bFGF supplementation increased the proliferation of PLC-MSCs in a dose-dependent manner and
40 ng/ml showed a high trophism effect on PLC-MSC’s growth. In the presence of bFGF, PLC-MSCs
acquired a small and well-defined morphology that reflect an active proliferative status. BFGF has
induced PLC-MSCs to achieve a shorter doubling time (45 hrs) as compared to the non-supplemented
PLC-MSCs culture (81 hrs). Furthermore, bFGF impelled PLC-MSCs into cell cycle machinery where
a substantial fraction of cells was driven to S and G2/M phases. Amongst, 36 screened cytokines, bFGF
had only altered the secretion of IL-8, IL-6, TNFR1, MMP3 and VEGF. Conclusion:The present study
showed that bFGF supplementation promotes the growth of PLC-MSCs without significantly deviating
from the standard criteria of MSCs. Thus, bFGF could be considered as a potential mitogen to facilitate
the large-scale production of PLC-MSCs.
Introduction: Immune response against viral infections and tumors not only requires the recruitment of immune cells but also cytokines. Cytokine dysregulation is associated with inflammatory diseases such as cancer, autoimmune diseases, infections and allergy. Intake of fruit and vegetables are known not only to reduce inflammation but may also provide protection against various diseases. Methods: Effects of selected fruits and herbs on cytokines profile of IL-8, IL-1β, IL-6, IL-10, TNF and IL-12p70 were examined using the CBA flow cytometric assay. Peripheral blood mononuclear cells (PBMC) obtained from blood samples of twelve healthy subjects aged 20 to 30 years [males = 6 and females = 6] were treated with papaya, mata kucing, dang shen and pu-erh tea, respectively, for 6 and 48 hours at various concentrations. In vivo effects was further tested on healthy volunteers [males = 2, females = 4] by 2-days consumption of papaya following 2-days washout period without papaya. The diet of volunteers was controlled with fixed meals. Results:In vitro results after 6 hours of culture showed that papaya-treated PBMC significantly increased IL-8, IL-1β and IL-6 but reduced IL-10. Mata kucing-treated PBMC significantly increased IL-8 but reduced IL-6 while pu-erh tea significantly reduced IL-8, IL-1β, IL-6 and TNF. Cytokine analysis for dang shen-treated PBMC was only conducted at 48 hours. After 48 hours, papaya extract significantly reduced IL-8, IL-6 (8000 μg/ml), IL-10 and TNF. Significant increase of IL-6 was observed at 4000 and 16000 μg/ml. Mata kucing extract significantly increased IL-1β, IL-6 but reduced TNF. Significant increase of TNF was observed at 16000 μg/ml. Dang shen and pu-erh tea reduced IL-8, IL-1β, IL-6, IL-10 and TNF. However, in vivo papaya consumption did not show any significant changes and levels were low. Conclusion: This study showed fruits such as papaya and mata kucing had both stimulatory and inhibitory effect on various pro-inflammatory cytokines while effect of herbs such as dang shen and pu-erh tea were inhibitory. Immunomodulatory studies of natural food such as fruits and herbs may provide better understanding and subsequently improve management of inflammatory diseases.
The immune system responds to stimulus by activation/increase or inhibition/decrease in activities. These immu-nomodulatory effects may be triggered by various factors in the environment including cytokines, hormones and growth factors, as well as flavonoids, antioxidants and various antigens in food and the environment. Immunosup-pression has a direct effect on the capacity of the immune system to fight against infection and cancer formation. A pro-inflammatory response, however, may induce further progression of tumours that had formed. Inflammation is also associated with many chronic illnesses including pain. The suppressive effects from phytochemicals have been shown in the potential to reduce T-lymphocyte proliferation in vitro and in vivo. Studies have demonstrated inhibi-tion of pro-inflammatory cytokines from flavonoid such as naringenin, green tea polyphenol extract, encapsulated fruit and vegetable juice powder concentrate. Feijoa sellowiana Berg var. coolidge fruit juice consumption exerted anti-inflammatory activity on edema-induced mice within first hour of treatment while agipenin, a natural flavonoid reduced neuroinflammation by protection against damage from dendritic cells stimulated T cells in experimental autoimmune encephalomyelitis mouse models. Dietary polyphenols were found to exert a regulatory role on den-dritic cell function. Our own study showed immunosuppressive effect from increased T regulatory cells from papaya consumption. Increased regulatory cells are associated with cancer conditions. On the other hand, grape juice con-sumption mobilized gamma–delta T cells. Ginseng berry extract increased pro-inflammatory molecules in dendritic cells in the spleen while polysaccharide fractions from Momorica charantia, an edible medicinal vegetable increased various immune indexes. Fruits may also have endo-immunomodulatory function causing differential effects in male and female. Sex hormones can influence immune changes based on sex as seen in increased NK cells in males and antibodies in females. We observed a population of CD4-CD45RA-CD69+CD25- cells was significantly lower in males. However, none of these studies have been directly conducted on cancers. Investigation into this area may help improve decision making in cancer management.
Our preliminary screening has shown that curcumin derivative BDMC33 [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] exerted promising nitric oxide inhibitory activity in activated macrophages. However, the molecular basis and mechanism for its pharmacological action is yet to be elucidated. The aim of this study was to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. Our current study demonstrated that BDMC33 inhibits the secretion of major pro-inflammatory mediators in stimulated macrophages, and includes NO, TNF-α and IL-1β through interference in both nuclear factor kappaB (NF-κB) and mitogen activator protein kinase (MAPK) signaling cascade in IFN-γ/LPS-stimulated macrophages. Moreover, BDMC33 also interrupted LPS signaling through inhibiting the surface expression of CD-14 accessory molecules. In addition, the inhibitory action of BDMC33 not only restricted the macrophages cell (RAW264.7), but also inhibited the secretion of NO and TNF-α in IFN-γ/LPS-challenged microglial cells (BV-2). The experimental data suggests the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases.