Blueberry Counteracts BV-2 Microglia Morphological and Functional Switch after LPS Challenge

Microglia, the innate immune cells of the CNS, respond to brain injury by activating and modifying their morphology. Our study arises from the great interest that has been focused on blueberry (BB) for the antioxidant and pharmacological properties displayed by its components. We analyzed the influence of hydroalcoholic BB extract in resting or lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. BB exerted a protective effect against LPS-induced cytotoxicity, as indicated by cell viability. BB was also able to influence the actin cytoskeleton organization, to recover the control phenotype after LPS insult, and also to reduce LPS-driven migration. We evaluated the activity of Rho and Rac1 GTPases, which regulate both actin cytoskeletal organization and migratory capacity. LPS caused an increase in Rac1 activity, which was counteracted by BB extract. Furthermore, we demonstrated that, in the presence of BB, mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α decreased, as did the immunofluorescence signal of iNOS, whereas that of Arg-1 was increased. Taken together, our results show that, during the inflammatory response, BB extract shifts the M1 polarization towards the M2 phenotype through an actin cytoskeletal rearrangement. Based on that, we might consider BB as a nutraceutical with anti-inflammatory activities.

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Modulation of Actin network and Tau phosphorylation by HDAC6 ZnF UBP domain

10.1101/702571 ◽

2019 ◽

Cited By ~ 3

Author(s):

Abhishek Ankur Balmik ◽

Shweta Kishor Sonawane ◽

Subashchandrabose Chinnathambi

Keyword(s):

Nuclear Localization ◽

Tau Phosphorylation ◽

Actin Network ◽

Cytoskeletal Organization ◽

Protein Tau ◽

Cytoskeleton Organization ◽

Actin Cytoskeleton Organization ◽

Aggresome Formation ◽

Gsk 3Β

AbstractMicrotubule-associated protein Tau undergoes aggregation in Alzheimer’s disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits polyubiquitinated aggregates to the motor protein dynein. Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemistry. Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre. Our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases.

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DietaryN-acetylcysteine supplementation alleviates liver injury in lipopolysaccharide-challenged piglets

British Journal Of Nutrition ◽

10.1017/s0007114513002171 ◽

2013 ◽

Vol 111 (1) ◽

pp. 46-54 ◽

Cited By ~ 34

Author(s):

Dan Yi ◽

Yongqing Hou ◽

Lei Wang ◽

Binying Ding ◽

Zhengguo Yang ◽

...

Keyword(s):

Liver Injury ◽

Heat Shock Protein 70 ◽

Basal Diet ◽

Control Group ◽

Saline Injection ◽

Antioxidative Capacity ◽

Blood Samples ◽

Lps Challenge ◽

Tnf Α ◽

Pro Inflammatory Cytokines

The present study was carried out to determine whetherN-acetylcysteine (NAC) could modulate liver injury in a lipopolysaccharide (LPS)-challenged piglet model. For this purpose, eighteen piglets were randomly assigned to the control, LPS or NAC group. Piglets in the control and LPS groups were fed a basal diet, whereas those in the NAC group were fed the basal diet supplemented with 500 mg/kg NAC. On days 10, 13 and 20 of the trial, the LPS- and NAC-treated piglets were intraperitoneally administered LPS (100 μg/kg body weight), while the control group was administered the same volume of saline. On day 20 of the trial, blood samples were obtained 3 h after LPS or saline injection. On day 21, the piglets were killed to collect liver samples. Dietary NAC supplementation attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, in the LPS-challenged piglets, the activities of alanine aminotransferase and aspartate aminotransferase and the concentrations of H2O2, TNF-α, IL-6 and PGE2were dramatically increased in the plasma and the activity of superoxide dismutase in the plasma and that of glutathione peroxidase in the liver were significantly decreased. The LPS challenge also increased the concentration of AMP and the ratio of AMP:ATP, but decreased adenylate energy charges and the levels of ATP and ADP. These adverse effects of the LPS challenge were ameliorated by NAC supplementation. Moreover, NAC inhibited the LPS-induced increases in the abundance of liver heat shock protein 70 and NF-κB proteins. In conclusion, these results suggest that dietary NAC supplementation alleviates LPS-induced liver injury by reducing the secretion of pro-inflammatory cytokines, increasing the antioxidative capacity and improving energy metabolism.

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The Effect of Allicin on Innate Immune Genes of Common Carp (Cyprinus carpio L)

Journal of Applied Biotechnology ◽

10.5296/jab.v4i1.8281 ◽

2015 ◽

Vol 4 (1) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Jean Fall ◽

Mahmoud Tanekhy

Keyword(s):

Inflammatory Diseases ◽

Head Kidney ◽

Innate Immune ◽

Therapeutic Effects ◽

Immune Genes ◽

Glucose Levels ◽

Tnf Α ◽

Innate Immune Genes ◽

The Impact ◽

Pro Inflammatory Cytokines

<p>Garlic is known to possess a vast variety of biological functions. It was reported to be ana a antimicrobial, antithrombotic, anticacer, antioxidant and could improve the immune-system as well as had the capacity to lower serum lipid and glucose levels. The impact of allicin on signaling pathways still needs to be investigated and reports about its effect on cytokine production are inconsistent. In the present study, we investigated the inﬂuence of allicin on several carp genes and checked the immediate response of these genes. Direct p-regulation of pro-inflammatory cytokines as IL-1β, TNF-α, IL-10, TLR3, and INF-α, INFγ1 was observed after stimulation of carp head kidney (HK) cells with allicin extract. These results strongly indicate that allicin is responsible for the anti-inﬂammatory effects. Further, the results suggest that there are potential therapeutic effects of allicin on chronic inﬂammatory diseases. These effects need more investigations in aquaculture industries.</p>

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Inflammatory Properties and Adjuvant Potential of Synthetic Glycolipids Homologous to Mycolate Esters of the Cell Wall of Mycobacterium tuberculosis

Journal of Innate Immunity ◽

10.1159/000450955 ◽

2016 ◽

Vol 9 (2) ◽

pp. 162-180 ◽

Cited By ~ 15

Author(s):

Hermann Giresse Tima ◽

Juma''a Raheem Al Dulayymi ◽

Olivier Denis ◽

Pauline Lehebel ◽

Klarah Sherzad Baols ◽

...

Keyword(s):

Cell Wall ◽

Innate Immune System ◽

Complex Mixture ◽

Innate Immune ◽

Oxygen Species ◽

Subunit Vaccines ◽

Mycolic Acids ◽

Trehalose Dimycolate ◽

Tnf Α ◽

Pro Inflammatory Cytokines

The cell wall of mycobacteria is characterised by glycolipids composed of different classes of mycolic acids (MAs; alpha-, keto-, and methoxy-) and sugars (trehalose, glucose, and arabinose). Studies using mutant Mtb strains have shown that the structure of MAs influences the inflammatory potential of these glycolipids. As mutant Mtb strains possess a complex mixture of glycolipids, we analysed the inflammatory potential of single classes of mycolate esters of the Mtb cell wall using 38 different synthetic analogues. Our results show that synthetic trehalose dimycolate (TDM) and trehalose, glucose, and arabinose monomycolates (TMM, GMM, and AraMM) activate bone marrow-derived dendritic cells in terms of the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species, upregulation of costimulatory molecules, and activation of NLRP3 inflammasome by a mechanism dependent on Mincle. These findings demonstrate that Mincle receptor can also recognise pentose esters and seem to contradict the hypothesis that production of GMM is an escape mechanism used by pathogenic mycobacteria to avoid recognition by the innate immune system. Finally, our experiments indicate that TMM and GMM, as well as TDM, can promote Th1 and Th17 responses in mice in an OVA immunisation model, and that further analysis of their potential as novel adjuvants for subunit vaccines is warranted.

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Modulation of Actin Network and Tau Phosphorylation by HDAC6 ZnF UBP Domain

10.21203/rs.3.rs-78228/v1 ◽

2020 ◽

Author(s):

Balmik Ankur Balmik ◽

Shweta Kishor Sonawane ◽

Subashchandrabose Chinnathambi

Keyword(s):

Nuclear Localization ◽

Tau Phosphorylation ◽

Actin Network ◽

Cytoskeletal Organization ◽

Protein Tau ◽

Cytoskeleton Organization ◽

Actin Cytoskeleton Organization ◽

Aggresome Formation ◽

Gsk 3Β

Abstract Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits polyubiquitinated aggregates to the motor protein dynein. Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemistry. Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre (MTOC). Our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases.

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Pro-inflammatory cytokine and acute phase protein responses to low-dose lipopolysaccharide (LPS) challenge in pigs

Animal Science ◽

10.1079/asc200665 ◽

2006 ◽

Vol 82 (4) ◽

pp. 527-534 ◽

Cited By ~ 18

Author(s):

S. Llamas Moya ◽

L. Boyle ◽

P. B. Lynch ◽

S. Arkins

Keyword(s):

Gender Differences ◽

Acute Phase ◽

Inflammatory Cytokine ◽

Low Dose ◽

Acute Phase Protein ◽

Plasma Concentrations ◽

Lps Challenge ◽

Tnf Α ◽

Phase Protein ◽

Pro Inflammatory Cytokines

AbstractThe objective of this study was to establish the pro-inflammatory cytokine and acute phase protein responses to low-dose lipopolysaccharide (LPS) challenge in pigs and to determine whether these immune parameters could also be measured in saliva. Possible gender differences in the acute phase reaction were also assessed. At 6 weeks of age, 24 male and 24 female pigs were injected intraperitoneally with a single dose of 0 or 5 μg/kg live weight (LW) of LPS fromEscherichia coli(treatment). Matched saliva and blood samples were taken at 0, 2, 4, 8, 12 or 24 h after treatment administration. Samples were analysed for concentrations of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), the acute phase proteins C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), and cortisol. Low-dose LPS administration increased plasma levels of TNF-α (P<0·001), CRP (P<0·05) and SAA (P<0·05) but did not affect plasma concentrations of IL-1β or Hp (P>0·1). Treatment by time interactions showed that plasma levels of TNF-α and CRP in LPS-treated pigs peaked at 2 h (P<0·001) and 12 h (P<0·01), respectively. Low-dose LPS injection tended to increase plasma concentrations of cortisol (P=0·056) and the response to LPS differed between genders (P<0·05), with females showing higher cortisol responsiveness to the challenge (P<0·01). Males showed higher levels of both cytokines regardless of the treatment (P<0·05), probably due to the inhibition of cytokine synthesis by cortisol. Concentrations of both pro-inflammatory cytokines were consistently detectable in saliva and were present in higher concentrations than in plasma (P<0·001). Hence, plasma TNF-α, CRP and SAA are useful indicators of sub-acute inflammation/infection in pigs as simulated by a low-dose LPS challenge and gender differences exist in the pro-inflammatory cytokine response after a low dose of LPS.

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MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock

Journal of Experimental Medicine ◽

10.1084/jem.20051794 ◽

2005 ◽

Vol 203 (1) ◽

pp. 131-140 ◽

Cited By ~ 284

Author(s):

Qun Zhao ◽

Xianxi Wang ◽

Leif D. Nelin ◽

Yongxue Yao ◽

Ranyia Matta ◽

...

Keyword(s):

Map Kinase ◽

Endotoxic Shock ◽

Innate Immune ◽

Innate Immune Responses ◽

Wild Type ◽

Kinase Activation ◽

Lps Challenge ◽

Map Kinase Phosphatase ◽

Tnf Α ◽

Severe Hypotension

Septic shock is a leading cause of morbidity and mortality. However, genetic factors predisposing to septic shock are not fully understood. Excessive production of proinflammatory cytokines, particularly tumor necrosis factor (TNF)-α, and the resultant severe hypotension play a central role in the pathophysiological process. Mitogen-activated protein (MAP) kinase cascades are crucial in the biosynthesis of proinflammatory cytokines. MAP kinase phosphatase (MKP)-1 is an archetypal member of the dual specificity protein phosphatase family that dephosphorylates MAP kinase. Thus, we hypothesize that knockout of the Mkp-1 gene results in prolonged MAP kinase activation, augmented cytokine production, and increased susceptibility to endotoxic shock. Here, we show that knockout of Mkp-1 substantially sensitizes mice to endotoxic shock induced by lipopolysaccharide (LPS) challenge. We demonstrate that upon LPS challenge, Mkp-1−/− cells exhibit prolonged p38 and c-Jun NH2-terminal kinase activation as well as enhanced TNF-α and interleukin (IL)-6 production compared with wild-type cells. After LPS challenge, Mkp-1 knockout mice produce dramatically more TNF-α, IL-6, and IL-10 than do wild-type mice. Consequently, Mkp-1 knockout mice develop severe hypotension and multiple organ failure, and exhibit a remarkable increase in mortality. Our studies demonstrate that MKP-1 is a pivotal feedback control regulator of the innate immune responses and plays a critical role in suppressing endotoxin shock.

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Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000520 ◽

2020 ◽

Vol 90 (1-2) ◽

pp. 103-112 ◽

Cited By ~ 1

Author(s):

Michael J. Haas ◽

Marilu Jurado-Flores ◽

Ramadan Hammoud ◽

Victoria Feng ◽

Krista Gonzales ◽

...

Keyword(s):

Endothelial Cells ◽

Ascorbic Acid ◽

Coronary Artery ◽

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Culture Media ◽

Cytokine Secretion ◽

Human Coronary Artery ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

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Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽

10.3390/nu11112794 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2794 ◽

Cited By ~ 8

Author(s):

Cao ◽

Chen ◽

Ren ◽

Zhang ◽

Tan ◽

...

Keyword(s):

Western Blot ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Blot Analysis ◽

Western Blot Analysis ◽

Inflammatory Responses ◽

Raw264.7 Macrophages ◽

Tnf Α ◽

Autophagy Inhibition ◽

Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

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233 NaturSafe® supplementation mitigates some aspects of the acute phase immune response to a lipopolysaccharide (LPS) challenge in weaned beef calves

Journal of Animal Science ◽

10.1093/jas/skaa054.199 ◽

2020 ◽

Vol 98 (Supplement_3) ◽

pp. 117-117

Author(s):

Nicole C Burdick Sanchez ◽

Jeffery A Carroll ◽

Paul R Broadway ◽

Tom S Edrington ◽

Ilkyu Yoon ◽

...

Keyword(s):

Acute Phase ◽

Treatment Time ◽

Sickness Behavior ◽

Serum Cortisol ◽

Post Challenge ◽

Serum Samples ◽

Lps Challenge ◽

Time Interaction ◽

Tnf Α ◽

Monitoring Devices

Abstract This study was conducted to determine if feeding calves NaturSafe would reduce the acute phase response (APR) to lipopolysaccharide (LPS) challenge. Crossbred steers (n=32; 274±2 kg) were randomly allotted to two treatment diets: 1) Control, fed a standard receiving ration, and 2) NaturSafe, fed the Control ration supplemented with NaturSafe at 12 g/hd/d (NaturSafe®, Diamond V). On d22, steers were fitted with indwelling jugular catheters and rectal temperature monitoring devices and placed in individual stalls. On d23, steers were challenged i.v. with 0.25 µg/kg BW LPS. Serum samples were collected and sickness behavior scores (SBS) recorded at 0.5-h intervals from -2 to 8h and at 24h relative to LPS challenge. Rectal temperatures were greater (P=0.01) in NaturSafe compared to Control steers for the following time intervals following LPS challenge: 6 to 11h, 13h, 15 to 20h, and 22 to 24h. Additionally, SBS were reduced (P< 0.01) in NaturSafe compared to Control steers. White blood cell concentrations were greater (P=0.05) in NaturSafe compared to Control steers prior to the LPS challenge, yet the response to LPS did not differ between treatments (P >0.05). A treatment × time interaction for serum cortisol concentrations (P< 0.01) showed an increase at 0.5 and 2h post-challenge but a reduction at 3h in NaturSafe compared to Control steers. Additionally, fibrinogen was greater (P< 0.01) in NaturSafe compared to Control steers. There was a treatment × time interaction (P< 0.01) for TNF-α where concentrations were reduced from 1 to 2h post-challenge in NaturSafe compared to Control steers. Serum IL-6 tended (P=0.09) to show a reduction in serum concentrations in NaturSafe compared to Control steers. There was a tendency (P=0.07) for a treatment × time interaction for IFN-γ. Overall these data suggest a priming effect of NaturSafe on the innate immune system of steers, resulting in an attenuated APR to the LPS challenge.

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