Transient Knock Down of Grp78 Reveals Roles in Serum Ferritin Mediated Pro-inflammatory Cytokine Secretion in Rat Primary Activated Hepatic Stellate Cells

Wang, Chi Mei; Li, Shan Jen; Wu, Chi Hao; Hu, Chien Ming; Cheng, Hui; Chang, Jung Su

doi:10.7314/apjcp.2014.15.2.605

Cited by 14 publications

(10 citation statements)

References 23 publications

(23 reference statements)

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“…GRP78 has been shown to inhibit the production of pro-inflammatory cytokines (TNF-α, IL-6 and IFN-β) induced by lipopolysaccharide (LPS) in bone marrow-derived dendritic cells (BMDCs) and bone-marrow-derived macrophages (BMDMs) [ 64 ]. Additionally, transient knockdown of GRP78 has been shown to abolish the secretion of serum ferritin mediated pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in rat primary activated hepatic stellate cells [ 65 ]. If GRPs are essential chaperones for the protection of cells, their elimination could result in detrimental effects on various biological functions.…”

Section: Discussionmentioning

confidence: 99%

Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury

Shologu

Scully

Laffey

et al. 2018

IJMS

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Alveolar epithelial dysfunction induced by hypoxic stress plays a significant role in the pathological process of lung ischemia-reperfusion injury (IRI). Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in exerting protective immunomodulatory effects, thereby reducing airway inflammation in several pulmonary diseases. Aim: This study assesses the protective effects of MSC secretome from different cell sources, human bone marrow (BMSC) and adipose tissue (ADSC), in attenuating hypoxia-induced cellular stress and inflammation in pulmonary epithelial cells. Methods: Pulmonary epithelial cells, primary rat alveolar epithelial cells (AEC) and A549 cell line were pre-treated with BMSC, or ADSC conditioned medium (CM) and subjected to hypoxia for 24 h. Results: Both MSC-CM improved cell viability, reduced secretion of pro-inflammatory mediators and enhanced IL-10 anti-inflammatory cytokine production in hypoxic injured primary rat AECs. ADSC-CM reduced hypoxic cellular injury by mechanisms which include: inhibition of p38 MAPK phosphorylation and nuclear translocation of subunits in primary AECs. Both MSC-CM enhanced translocation of Bcl-2 to the nucleus, expression of cytoprotective glucose-regulated proteins (GRP) and restored matrix metalloproteinases (MMP) function, thereby promoting repair and cellular homeostasis, whereas inhibition of GRP chaperones was detrimental to cell survival. Conclusions: Elucidation of the protective mechanisms exerted by the MSC secretome is an essential step for maximizing the therapeutic effects, in addition to developing therapeutic targets-specific strategies for various pulmonary syndromes.

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Section: Discussionmentioning

confidence: 99%

Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury

Shologu

Scully

Laffey

et al. 2018

IJMS

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“…Hepcidin plays a key role in the innate and adaptive immunities [ 13 ]. Elevated serum ferritin can function as a proinflammatory modulator by upregulating IL-1β, tumor necrosis factor (TNF)-α, and nitric oxide (NO) transcriptional activity [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Ferritin Is Inversely Correlated with Testosterone in Boys and Young Male Adolescents: A Cross-Sectional Study in Taiwan

et al. 2015

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ObjectiveThe transition from childhood to teenaged years is associated with increased testosterone and a decreased iron status. It is not clear whether higher testosterone levels cause the decreased iron status, and to what extent, obesity-related inflammation influences the iron-testosterone relationship. The aim of the present study was to examine relationships of testosterone, iron status, and anti-/proinflammatory cytokines in relation to nutritional status in boys and young adolescent Taiwanese males.MethodsIn total, 137 boys aged 7~13 yr were included. Parameters for obesity, the iron status, testosterone, and inflammatory markers were evaluated.ResultsOverweight and obese (ow/obese) boys had higher mean serum testosterone, interleukin (IL)-1β, and nitric oxide (NO) levels compared to their normal-weight counterparts (all p<0.05). Mean serum ferritin was slightly higher in ow/obese boys compared to normal-weight boys, but this did not reach statistical significance. A multiple linear regression showed that serum ferritin (β = -0.7470, p = 0.003) was inversely correlated with testosterone, while serum IL-10 (β = 0.3475, p = 0.009) was positively associated with testosterone after adjusting for covariates. When normal-weight boys were separately assessed from ow/obesity boys, the association between testosterone and serum ferritin became stronger (β = -0.9628, p<0.0001), but the association between testosterone and IL-10 became non-significant (β = 0.1140, p = 0.4065) after adjusting for covariates. In ow/obese boys, only IL-10 was weakly associated with serum testosterone (β = 0.6444, p = 0.051) after adjusting for age.ConclusionsTestosterone and serum ferritin are intrinsically interrelated but this relationship is weaker in ow/obese boys after adjusting for age.

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“…Secretion of pro-inflammatory cytokines such as IL1β, IL6 and TNFα has been noted in activated rat HSCs [31] and the presence of inflammation was then examined in liver samples after DMN treatment. As seen in Fig.…”

Section: Resultsmentioning

confidence: 99%

Acute liver injury induced by low dose dimethylnitrosamine alters mediators of hepatic vascular flow

et al. 2014

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Alterations in liver vascular tone play an important role in chronic liver disease. The hepatic stellate cell (HSC) and mediators such as nitric oxide (NO) and hydrogen sulfide (H2S) have been implicated in regulation of vascular tone and intra-hepatic pressure. Though these have been studied in chronic liver damage, changes in response to acute liver injury induced by hepatotoxins such as dimethyl nitrosamine are not well understood. Liver injury was induced in mice by a single intra-peritoneal injection of dimethylnitrosamine (DMN), following which animals were sacrificed at 24, 48 and 72 h. Changes in vascular mediators such as NO and H2S as well as stellate cell activation was then examined. It was found that a single low dose of DMN in mice is sufficient to induce activation of hepatic stellate cells within 24 h, accompanied by oxidative stress, compromised metabolism of H2S and decreased levels of the von Willebrand factor (vWF) cleaving protease; a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), which functions in intravascular thrombosis. A suppression of hepatic NO levels is also initiated at this time point, which progresses further and is sustained up to 72 h, at which point the HSC activation is still present. Compromised levels of ADAMTS13 and H2S metabolism however, begin to recover by 48 h and are almost similar to control by 72 h. In conclusion, these data suggest that even moderate acute insults in the liver can have far reaching consequences on a number of mediators of vascular flow in the liver.

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Transient Knock Down of Grp78 Reveals Roles in Serum Ferritin Mediated Pro-inflammatory Cytokine Secretion in Rat Primary Activated Hepatic Stellate Cells

Cited by 14 publications

References 23 publications

Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury

Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury

Serum Ferritin Is Inversely Correlated with Testosterone in Boys and Young Male Adolescents: A Cross-Sectional Study in Taiwan

Acute liver injury induced by low dose dimethylnitrosamine alters mediators of hepatic vascular flow

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