scholarly journals Gadolinium Chloride Inhibits the Production of Liver Interleukin-27 and Mitigates Liver Injury in the CLP Mouse Model

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jing Fan ◽  
Miao He ◽  
Chuan-Jiang Wang ◽  
Mu Zhang
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Severe Infection ◽  
Peritoneal Macrophages ◽  
Gadolinium Chloride ◽  
Liver Macrophages ◽  
M1 Polarization ◽  
Liver Macrophage ◽  
Tnf Α ◽  
Cell Proportion

Background. Liver macrophages play an important regulatory role in the inflammatory response of liver injury after severe infection. Interleukin- (IL-) 27 is an inflammatory cytokine that plays an important role in diseases caused by bacterial infection. However, the relationship between IL-27 and liver macrophages in liver injury after severe infection is not yet clear. Methods. A cecal ligation puncture (CLP) model was established in wild-type (WT) and IL-27 receptor- (WSX-1-) deficient (IL-27r-/-) mice, and recombinant IL-27 and gadolinium chloride (GdCl3) were injected into WT mice in the designated groups. The serum and liver IL-27, IL-6, tumor necrosis factor alpha (TNF-α), and IL-1β expression levels were evaluated by ELISA, quantitative PCR, or Western blotting; serum ALT and AST were detected by detection kits; and the severity of liver damage was evaluated by hematoxylin and eosin staining and the TUNEL assay of the liver tissue from the different groups. Liver macrophage polarization was evaluated by immunofluorescence. In addition, the polarization of peritoneal macrophage was evaluated by flow cytometry. Results. The serum and liver IL-27 expression levels were elevated in WT mice after CLP-induced severe infection, which were consistent with the changes in HE scores in the liver tissue. The levels of serum ALT, AST, liver IL-6, TNF-α, and IL-1β mRNA and liver pathological injury scores were further increased when pretreated with recombinant IL-27 in WT mice, but these levels were decreased in IL-27r−/− mice after CLP-induced severe infection compared to WT mice. In WT mice pretreated with GdCl3, liver pathological scores, serum ALT and AST, TUNEL-positive cell proportion from liver tissues, liver IL-27 expression, and the liver macrophages M1 polarization proportion decreased after CLP; however, the serum IL-27, IL-6, TNF-α, and IL-1β levels and the pathological lung and kidney scores were not significantly changed. When supplemented with exogenous IL-27, the liver pathological scores, serum ALT, AST, TUNEL-positive cell proportion of liver tissues, liver IL-27 expression, and the liver macrophage M1 polarization proportion increased. The in vitro, IL-27 expression increased in peritoneal macrophages when stimulated with LPS. Recombinant IL-27 together with LPS promoted the elevations in IL-6, TNF-α, and IL-1β levels in supernatant and the M1 polarization of peritoneal macrophages. Conclusion. IL-27 is an important cytokine in the inflammatory response to liver injury after severe infection. The reduction of liver injury by gadolinium chloride in severe infection mice models may relate to the inhibition of liver IL-27 production. These changes may be mainly related to the decrease of liver macrophages M1 polarization. IL-27 may have a positive feedback on these macrophages.

scholarly journals S100A6 Promotes Inflammation and Infiltration of Mononuclear/Macrophages via the p-P38 and p-JNK Pathways in Acute Liver Injury

2021 ◽  
Author(s):  
He Tong ◽  
Li Wang ◽  
Kefan Zhang ◽  
Jing Shi ◽  
yongshuai Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
S100 Protein ◽  
Inflammatory Cells ◽  
Liver Cells ◽  
Danger Signal ◽  
Tnf Α

Abstract BackgroundThe phagocytic S100 protein, which mediates inflammatory responses and recruits inflammatory cells to sites of tissue damage, has long been known to be expressed in cells of myeloid origin. S100A6 belongs to the A group of the S100 protein family of Ca2+-binding proteins. Currently, the mechanism by which S100A6 mediates the inflammatory response and recruits inflammatory cells to the tissue injury site is unknown.MethodsA mouse model of carbon tetrachloride (CCl4)-induced acute liver injury (ALI) was established, and the transcriptomes of postinjury 2d and 5d liver tissues were sequenced. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) in the supernatant of the liver. Immunohistochemical analysis confirmed the expression of S100A6 in the liver cells. In vitro experiments proved the pro-inflammatory function of S100A6, and western blotting (WB) showed that the pathways were activated. The transwell experiment showed the infiltration of mononuclear/macrophages.ResultsWe found that S100A6 is highly expressed in liver cells during the most severe period of ALI, suggesting that it acts as an endogenous danger signal and has a pro-inflammatory function. In vitro, the mouse S100A6 recombinant protein was used to stimulate liver Kupffer cells to promote the secretion of TNF-α, IL-1β, IL-6, and IL-8. Further mechanistic experiments revealed that S100A6 acts as an endogenous danger signal to activate p-P38 and p-JNK downstream of the TLR4 and P65 pathways. Similarly, transcriptome data showed that S100A6 can activate the inflammatory response in Kuffer cells. WB revealed that S100A6 had no significant effect on cell apoptosis. To continue to explore the mechanism of monocyte/macrophage infiltration, we found that TNF-α stimulates liver cells as the main source of CCL2. TNF-α can initiate the p-P38 and p-JNK pathways of liver cells to produce CCL2, thereby recruiting the infiltration of mononuclear/macrophages. ConclusionsTaken together, S100A6 is an endogenous danger signal that mediates inflammatory responses and recruits inflammatory cells to sites of tissue damage.

Endogenous glucocorticoids released during acute toxic liver injury enhance hepatic IL-10 synthesis and release

1999 ◽  
Vol 276 (1) ◽  
pp. G199-G205 ◽  
Author(s):  
Mark G. Swain ◽  
Caroline Appleyard ◽  
John Wallace ◽  
Howard Wong ◽  
Tai Le
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Mrna Expression ◽  
Elevated Serum ◽  
Ru 486 ◽  
Tnf Α ◽  
Toxic Liver Injury ◽  
Acute Toxic

Endogenous glucocorticoids are known to play a role in the regulation of the inflammatory response possibly by modulating pro- and anti-inflammatory cytokine expression. We examined endogenous glucocorticoid secretion, hepatic damage, tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) mRNA expression and release in rats treated with carbon tetrachloride (CCl4) after treatment with vehicle or a glucocorticoid receptor antagonist (RU-486). Rats treated with CCl4 demonstrated striking elevations of plasma corticosterone levels. Inhibition of endogenous glucocorticoid activity by pretreatment with the glucocorticoid receptor antagonist RU-486 resulted in augmented CCl4-mediated hepatotoxicity, as reflected by histology and serum transaminase levels, which were independent of alterations in serum TNF-α levels or hepatic mRNA expression. CCl4 treatment resulted in enhanced hepatic IL-10 mRNA expression and elevated serum IL-10 levels, which were markedly attenuated by glucocorticoid receptor blockade. In summary, significant endogenous glucocorticoid release occurs during acute toxic liver injury in the rat and suppresses the inflammatory response independent of effects on TNF-α but possibly by upregulating hepatic IL-10 production.

Abstract 124: Sam68 Impedes the Recovery of Arterial Injury by Augmenting Inflammatory Response

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Shuling Han ◽  
Junlan Zhou ◽  
Baron T Arnone ◽  
Dauren Biyashev ◽  
Chan Boriboun ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Vascular Inflammation ◽  
Critical Role ◽  
Inflammatory Cells ◽  
Peritoneal Macrophages ◽  
Raw264.7 Macrophages ◽  
Tnf Α

Background: The role of Src-associated in mitosis 68 kDa (Sam68) in cardiovascular biology has not been studied. A recent report suggests that Sam68 suppresses TNF-α-induced NF-κB activation. Since NF-κB plays a critical role in vascular inflammation and injury via generation of inflammatory cytokines and recruitment of inflammatory cells, we sought to dissect the mechanism by which Sam68 regulates NF-κB signaling and its functional significance during vascular injury. Methods & Results: The endothelial denudation injury was induced in the carotid arteries of Sam68-/- and WT mice. Sam68-/- mice displayed an accelerated re-endothelialization and attenuated neointima hyperplasia, which was associated with a reduced number of macrophages and lowered expression of pro-inflammatory cytokines (i.e., TNF-α, IL-1β and IL-6) in the injured vessels. Importantly, the ameliorated vascular remodeling was recapitulated in WT mice after transplantation of bone marrow (BM) from Sam68-/- mice, suggesting beneficial role was attributed largely to BM-derived inflammatory cells. In cultured Raw264.7 macrophages, knockdown of Sam68 resulted in a significant reduction in the TNF-α-induced expression of TNF-α, IL-1β, and IL-6 and in the level of nuclear phospho-p65, indicating an attenuated NF-κB activation. These results were confirmed in peritoneal macrophages and macrophages differentiated from BM mononuclear cells of Sam68-/- and WT mice. To identify molecular mechanisms, Raw264.7 cells were treated with TNF-α and Vehicle, followed by Sam68 co-immunoprecipitation and mass-spec identification of Sam68-interacting proteins. Specifically, TNF-α treatment results in altered interactions of Sam68 with Filamin A (FLNA), a cytoskeleton protein known to be involved in NF-κB activation. Loss- and gain-of-function of Sam68 and FLNA suggest their mutual dependence in NF-κB activation and pro-inflammatory cytokine expression, and Sam68 is required for TRAF2-FLNA interaction. Conclusions: Our results for the first time suggest that Sam68 promotes pro-inflammatory response in injured arteries and impedes recovery, and this effect is attributed, in part, to the exaggerated NF-κB activity via Sam68-FLNA interaction and consequent TRAF2 stabilization.

scholarly journals Increments in cytokines and matrix metalloproteinases in skeletal muscle after injection of tissue-damaging toxins from the venom of the snakeBothrops asper

2002 ◽  
Vol 11 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Alexandra Rucavado ◽  
Teresa Escalante ◽  
Catarina F. P. Teixeira ◽  
Cristina María Fernándes ◽  
Cecilia Díaz ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Inflammatory Response ◽  
Experimental Model ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
Local Inflammatory Response ◽  
Mmp Inhibitor ◽  
Tnf Α ◽  
Factor Α

Envenomations by the snakeBothrops asperare characterized by prominent local tissue damage (i.e. myonecrosis), blistering, hemorrhage and edema. Various phospholipases A2and metalloproteinases that induce local pathological alterations have been purified from this venom. Since these toxins induce a conspicuous inflammatory response, it has been hypothesized that inflammatory mediators may contribute to the local pathological alterations described. This study evaluated the local production of cytokines and matrix metalloproteinases (MMPs) as a consequence of intramuscular injections of an Asp-49 myotoxic phospholipase A2(myotoxin III (MT-III)) and a P-I type hemorrhagic metalloproteinase (BaP1) isolated fromB. aspervenom. Both enzymes induced prominent tissue alterations and conspicuous increments in interleukin (IL)-1β, IL-6 and a number of MMPs, especially gelatinase MMP-9, rapidly after injection. In contrast, no increments in tumor necrosis factor-α (TNF-α) and interferon-γ were detected. In agreement, MT-III and BaP1 did not induce the synthesis of TNF-α by resident peritoneal macrophagesin vitro. Despite the conspicuous expression of latent forms of MMPs in muscle, evidenced by zymography, there were no increments in activated MMP-2 and only a small increase in activated MMP-9, as detected by a functional enzymatic assay. This suggests that MMP activity was regulated by a highly controlled activation of latent forms and, probably, by a concomitant synthesis of MMP inhibitors. Since no hemorrhage nor dermonecrosis were observed after injection of MT-III, despite a prominent increase in MMP expression, and since inflammatory exudate did not enhance hemorrhage induced by BaP1, it is suggested that endogenous MMPs released in the tissue are not responsible for the dermonecrosis and hemorrhage characteristic ofB. asperenvenomation. Moreover, pretreatment of mice with the peptidomimetic MMP inhibitor batimastat did not reduce myotoxic nor edema-forming activities of MT-III, suggesting that MMPs do not play a prominent role in the pathogenesis of these effects in this experimental model. It is concluded that MT-III and BaP1 induce a local inflammatory response associated with the synthesis of IL-1β, IL-6 and MMPs. MMPs do not seem to play a prominent role in the acute local pathological alterations induced by these toxins in this experimental model.

Mo1376 - Therapeutic Effects of Microrna-21 Depletion on Inflammatory Response in Liver Macrophages During Cholestatic Liver Injury

2018 ◽  
Vol 154 (6) ◽  
pp. S-1186-S-1187
Author(s):  
Keisaku Sato ◽  
Lindsey Kennedy ◽  
Thao Giang ◽  
Tianhao Zhou ◽  
Sugeily Ramos-Lorenzo ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Therapeutic Effects ◽  
Liver Macrophages ◽  
Cholestatic Liver Injury

scholarly journals Vibrio alginolyticus Triggers Inflammatory Response in Mouse Peritoneal Macrophages via Activation of NLRP3 Inflammasome

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinxin Wang ◽  
Qun Ding ◽  
Qiankun Yang ◽  
Hui Fan ◽  
Guili Yu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Peritoneal Macrophages ◽  
Vibrio Alginolyticus ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Caspase 1 ◽  
Tnf Α ◽  
Mouse Peritoneal Macrophages

Vibrio alginolyticus is a food-borne marine Vibrio that causes gastroenteritis, otitis media, otitis externa, and septicemia in humans. The pathogenic mechanisms of V. alginolyticus have previously been studied in aquaculture animals; however, the underlying mechanisms in mammals remain unknown. In this study, an in vitro model of mouse peritoneal macrophages infected with V. alginolyticus was established. qPCR results revealed that V. alginolyticus induced the transcription levels of various cytokines, including IL-1β, IL-12, IL-18, TNF-α, IL-17, IL-6, IFN-γ, and IL-10, and the secretion level of IL-1β is the most significant. Inhibition assays with Ac-YVAD-CHO (a caspase-1 inhibitor) and Z-VAD-FMK (a pan-caspase inhibitor) were conducted to determine whether caspase-1 or caspase-11 is involved in V. alginolyticus-triggered IL-1β secretion. Results showed that IL-1β secretion was partly inhibited by Ac-YVAD-CHO and absolutely blocked by Z-VAD-FMK. To explore the sensed pattern recognition receptors, several NLR family members and the AIM2 receptor were detected and many receptors were upregulated especially NLRP3. Moreover, the NLRP3 protein displayed a puncta-like surrounding cell nucleus, which signified that the NLRP3 inflammasome was activated in response to V. alginolyticus infection. Inhibition assays with glyburide and CA-074 methyl ester (K+ outflow inhibitor and cathepsin B inhibitor) blocked IL-1β secretion, which demonstrated the essential role of the NLRP3 inflammasome in inflammatory response. To better understand how V. alginolyticus affects IL-1β release, the NLRP3 inflammasome was detected with doses ranging from 0.1 to 10 MOIs and time periods ranging from 3 to 12 h. Results showed that V. alginolyticus-mediated NLRP3 inflammasome activation was in a time- and dose-dependent manner and IL-1β release peaked at MOI of 1 for 12 h. Most importantly, blocking the NLRP3 inflammasome with inhibitors and the use of NLRP3-/- and caspase-1/11-/- mice could attenuate pro-inflammatory cytokine secretion, such as IL-1β, IL-6, IL-12, and TNF-α. Taken together, our study first found that the NLRP3 inflammasome plays vital roles in V. alginolyticus triggered inflammatory response in mouse peritoneal macrophages. This may provide reference information for the development of potential anti-inflammatory treatments against V. alginolyticus infection.

Pro-Inflammatory and Pro-Coagulant Effects of Gemtuzumab Ozogamicin (Mylotarg®); Implications for the Development of VOD-Like Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2156-2156
Author(s):  
Johanna C. Bruneau ◽  
Aengus O’Marcaigh ◽  
Owen P. Smith
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Cell Line ◽  
Inflammatory Cytokines ◽  
De Novo ◽  
Sandwich Elisa ◽  
Haematopoietic Stem Cell ◽  
Cell Surface Expression ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Gemtuzumab Ozogomicin (GO) is a humanized IgG4 anti-CD33 monoclonal antibody covalently linked to the powerful antitumour antibiotic, calicheamicin. CD33 expression is found on myeloid (mature and immature), erythroid, megakaryocytic, and multipotent progenitors but is absent from normal CD34+ pluripotent haematopoietic stem cells and non-haematopoietic tissues. GO has been used successfully in de novo and refractory/relapsed CD33+ AML, and in other CD33+ leukaemias, including ALL - the main rationale being it selectively targets the CD33+ blast population while sparing the CD33– haematopoietic stem cell compartment. Although myelosuppression is the main toxicity seen in the vast majority of patients (>95%) receiving GO at doses ranging from 6 to 9mg/m2, it is the liver injury, especially veno-occlusive disease (VOD)-like syndrome, that is unique and the most significant drug-related toxicity observed. Previous studies have shown that patients who develop VOD-like syndrome have higher circulating levels of pro-inflammatory cytokines and reduced levels of the natural anti-coagulants protein C and anti-thrombin, suggesting that a pro-inflammatory and pro-coagulant state is induced in the liver, however no specific mechanism has been elucidated to account for the liver toxicity. One possible explanation is that GO binds to CD33+ Kupffer cells and/or other CD33+ cells residing in the hepatic sinusoids and in doing so induces state of pro-inflammation and pro-coagulation which in turn causes the sinusoidal fibrosis, centrilobular congestion, and hepatocyte necrosis, the histological hallmark of this process. To investigate this possibility, the CD33+ AML cell line, THP1, and the CD33– hepatocyte cell line, HepG2, were treated with increasing concentrations of GO. Secreted levels of the pro-inflammatory cytokines TNF-α and IL-8 were measured by sandwich ELISA. Cell surface expression levels of Tissue Factor (TF), the critical initiator of the pro-coagulation pathway, were analysed by flow cytometry. Cell proliferation was measured by the WST-1 assay. A statistically significant (P<0.001) pro-coagulant but not pro-inflammatory response was observed following GO exposure in both cell lines. THP1 cells showed upregulation of TF expression after 24 hour incubation with GO but no significant increase in TNF-α or IL-8 levels. Neither cell line showed a significant change in proliferation levels after treatment with GO. These results suggest that the initial response to GO treatment is pro-coagulant. After the first treatment, there will be fewer CD33+ blast cells, leaving more GO molecules free to ligate to CD33+ targets in the liver, therefore repeated administration of the drug increases the pro-coagulant state and perpetuates the liver injury. Continuous injury of the liver initiates an inflammatory response through autocrine and paracrine loops. This serves as the initiation signal for fibrosis. If the cycle of inflammation and coagulation proceeds unchecked, the fibrogenic cascade is continued leading to the development of VOD-like syndrome.

scholarly journals VSIG4(+) peritoneal macrophages induce apoptosis of double-positive thymocyte via the secretion of TNF-α in a CLP-induced sepsis model resulting in thymic atrophy

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Hae-Yun Cho ◽  
Yun Gyeong Yang ◽  
Youkyoung Jeon ◽  
Chae-Kwan Lee ◽  
InHak Choi ◽  
...  
Keyword(s):  
Severe Infection ◽  
Peritoneal Macrophages ◽  
Double Positive ◽  
Thymic Atrophy ◽  
Mhc Ii ◽  
Tnf Α ◽  
Double Positive Thymocyte ◽  
Thymocyte Apoptosis ◽  
Induced Apoptosis ◽  
Phenotypic Shift

AbstractThymic atrophy in sepsis is a critical disadvantage because it induces immunosuppression and increases the mortality rate as the disease progresses. However, the exact mechanism of thymic atrophy has not been fully elucidated. In this study, we discovered a novel role for VSIG4-positive peritoneal macrophages (V4(+) cells) as the principal cells that induce thymic atrophy and thymocyte apoptosis. In CLP-induced mice, V4(+) cells were activated after ingestion of invading microbes, and the majority of these cells migrated into the thymus. Furthermore, these cells underwent a phenotypic shift from V4(+) to V4(−) and from MHC II(low) to MHC II(+). In coculture with thymocytes, V4(+) cells mainly induced apoptosis in DP thymocytes via the secretion of TNF-α. However, there was little effect on CD4 or CD8 SP and DN thymocytes. V4(−) cells showed low levels of activity compared to V4(+) cells. Thymic atrophy in CLP-induced V4(KO) mice was much less severe than that in CLP-induced wild-type mice. In addition, V4(KO) peritoneal macrophages also showed similar activity to V4(−) cells. Taken together, the current study demonstrates that V4(+) cells play important roles in inducing immunosuppression via thymic atrophy in the context of severe infection. These data also suggest that controlling the function of V4(+) cells may play a crucial role in the development of new therapies to prevent thymocyte apoptosis in sepsis.

scholarly journals Ubiquitin fold modifier 1 activates NF-κB pathway by down-regulating LZAP expression in the macrophage of diabetic mouse model

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Xiaolei Hu ◽  
Hengyan Zhang ◽  
Yuan Song ◽  
Langen Zhuang ◽  
Qingqing Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Diabetic Mouse ◽  
Peritoneal Macrophages ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Factor Α ◽  
Necrosis Factor

Abstract Inflammatory response is closely related with the development of many serious health problems worldwide including diabetes mellitus (DM). Ubiquitin-fold modifer 1 (Ufm1) is a newly discovered ubiquitin-like protein, while its function remains poorly investigated, especially in inflammatory response and DM. In the present study, we analyzed the role of Ufm1 on inflammatory response in DM, and found that the proinflammatory cytokine levels (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β) and Ufm1 expression were highly increased both in the peritoneal macrophages of db/db mice and Raw264.7 cells induced by lipopolysaccharide (LPS). Western blot and luciferase reporter assay showed that NF-κB pathway was obviously activated in macrophages and the expression of LZAP, an inhibitor of NF-κB pathway, was down-regulated. With the LZAP knockdown plasmid and activation plasmid, we demonstrated that NF-κB/p65 activation was inhibited by LZAP in macrophages. The interaction of Ufm1 and LZAP was further proved with co-immunoprecipitation assay in HEK293 and Raw264.7 cells. The LZAP expression was also related with the presence of Ufm1 demonstrated by Ufm1 knockdown plasmid and activation plasmid. Besides that, we finally proved that the expression and activation of Ufm1 induced by LPS were regulated by JNK/ATF2 and JNK/c-Jun pathway with the use of SP600125. In conclusion, the present study demonstrated that Ufm 1 could activate NF-κB pathway by down-regulating LZAP in macrophage of diabetes, and its expression and activation were regulated by JNK/ATF2 and c-Jun pathway.

Sorghum Fermented by Aspergillus oryzae NK Enhances Inhibition of Vascular Inflammation in TNF-α-stimulated Human Aortic Smooth Muscle Cells

2018 ◽  
Vol 88 (5-6) ◽  
pp. 309-318
Author(s):  
Hae Seong Song ◽  
Jung-Eun Kwon ◽  
Hyun Jin Baek ◽  
Chang Won Kim ◽  
Hyelin Jeon ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Smooth Muscle Cells ◽  
Adhesion Molecule ◽  
Vascular Inflammation ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Tnf Α ◽  
Cox 2

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.

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