Wonhwa Lee

Polyphosphate elicits pro-inflammatory responses that are counteracted by activated protein C in both cellular and animal models.

See also Mutch NJ. Polyphosphate scores a hat trick in regulating host defense mechanisms. This issue, pp 1142–4.

Transforming Growth Factor β–induced Protein Promotes Severe Vascular Inflammatory Responses

RATIONALE Sepsis is a systemic inflammatory condition resulting from bacterial infections; it has a high mortality rate and limited therapeutic options. Despite extensive research into the mechanisms driving bacterial sepsis, the target molecules controlling vascular leakage are still largely unknown. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types, which is known to interact with integrins. OBJECTIVES The aim of this study was to determine the roles of TGFBIp in vascular proinflammatory responses, and the mechanisms of action driving these responses. METHODS Circulating levels of TGFBIp were measured in patients admitted to the hospital with sepsis, severe sepsis, and septic shock and in cecal ligation and puncture (CLP)-induced septic mice. Effects of TGFBIp knockout on CLP-induced septic mortality and effects of TGFBIp on multiple vascular proinflammatory responses were determined. MEASUREMENTS AND MAIN RESULTS Circulating levels of TGFBIp were significantly elevated compared with healthy controls, and were strongly correlated with disease severity. High blood TGFBIp levels were also observed in CLP-induced septic mice. The absence of the TGFBIp gene in mice attenuated CLP-induced sepsis. TGFBIp enhanced vascular proinflammatory responses including vascular permeability, adhesion and migration of leukocytes, and disruption of adherence junctions through interacting with integrin αvβ5. CONCLUSIONS Collectively, our findings demonstrate that the TGFBIp-αvβ5 axis can elicit severe inflammatory responses, suggesting it to be a potential target for development of diagnostics and therapeutics for sepsis.

Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models.

Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. In this study, we first investigated the possible barrier protective effects of WFA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice induced by high mobility group box 1 protein (HMGB1) and the associated signaling pathways. The barrier protective activities of WFA were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that WFA inhibited lipopolysaccharide (LPS)-induced HMGB1 release and HMGB1-mediated barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of leukocytes to human endothelial cells. WFA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that WFA suppressed the production of interleukin 6, tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB) by HMGB1. Collectively, these results suggest that WFA protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

Vascular anti-inflammatory effects of curcumin on HMGB1-mediated responses in vitro

Aim and objectiveHigh mobility group box 1 (HMGB1) protein up-regulates proinflammatory cytokines in several inflammatory diseases. Curcumin is a polyphenol responsible for the yellow color of the curry spice turmeric. It possesses diverse pharmacological properties such as anti-inflammatory, anti-oxidant, anti-proliferative and anti-angiogenic activities. However, the effects of curcumin on HMGB1-mediated proinflammatory responses have not been studied.MethodsThe anti-inflammatory activities of curcumin were determined by measuring solute flux, leukocyte adhesion and migration and activation of proinflammatory proteins in HMGB1-activated human umbilical vein endothelial cells.ResultsCurcumin inhibited the release of HMGB1 by lipopolysaccharide (LPS)- and HMGB1-mediated barrier disruption, neutrophil adhesion and migration, and expression of cell adhesion molecules. Further studies revealed that curcumin down-regulated the cell surface receptor of HMGB1 in human endothelial cells.ConclusionThese findings suggest that curcumin exerts anti-inflammatory effects in HMGB1-mediated proinflammatory responses, endorsing its usefulness as therapy for vascular inflammatory diseases.

Endocan Elicits Severe Vascular Inflammatory Responses In Vitro and In Vivo

Endocan is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines. The aim of this study was to evaluate the effects of endocan on proinflammatory responses and on septic mice and underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) or mice were exposed to lipopolysaccharide (LPS) or endocan with or without neutralizing endocan antibody. Mice were subjected to cecal ligation and puncture (CLP) surgery with or without neutralizing endocan antibody. Endocan was highly released by LPS and it enhanced proinflammatory responses. In a CLP‐induced sepsis model, endocan was also highly released, but this release was prevented by administration of neutralizing endocan antibody. Circulating levels of endocan measured in patients admitted to the intensive care unit with sepsis were significantly elevated compared with control donors. Furthermore, the administration of endocan antibody reduced CLP‐induced sepsis mortality. This study shows endocan can elicit severe inflammatory responses and inhibiting endocan release offers a potential strategy for treating sepsis. J. Cell. Physiol. 229: 620–630, 2014.

Anti-inflammatory Effects of Baicalin, Baicalein, and Wogonin In Vitro and In Vivo

Here, three structurally related polyphenols found in the Chinese herb Huang Qui, namely baicalin, baicalein, and wogonin, were examined for its effects on inflammatory responses by monitoring the effects of baicalin, baicalein, and wogonin on lipopolysaccharide (LPS)-mediated vascular inflammatory responses. We found that each compound inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to human endothelial cells. Each compound induced potent inhibition of phorbol-12-myristate 13-acetate and LPS-induced endothelial cell protein C receptor shedding. It also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Furthermore, each compound suppressed the production of tumor necrosis factor-α or interleukin-6 and the activation of nuclear factor-κB or extracellular regulated kinases 1/2 by LPS. Moreover, treatment with each compound resulted in reduced LPS-induced lethal endotoxemia. These results suggest that baicalin, baicalein, and wogonin posses anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

Dermoscopy can be useful in differentiating scalp psoriasis from seborrhoeic dermatitis

Background  Psoriasis and seborrhoeic dermatitis are common erythematous‐squamous dermatoses that may present with scaly erythematous patches on the scalp. Owing to the similar clinicopathological features of these dermatoses, their differentiation poses a diagnostic challenge, particularly when the lesions on the scalp are isolated.

Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro and in vivo.

Oleanolic acid (OA) is a triterpenoid known for its anti-inflammatory and anti-cancer properties; however, the anti-inflammatory effects of OA on lipopolysaccharide (LPS)-mediated pro-inflammatory responses have not been studied. Here, we first investigated the possible anti-inflammatory effects of OA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by LPS and the associated signaling pathways. We found that OA inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to HUVECs. OA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocyte migration in vivo. Further studies revealed that OA suppressed the production of tumor necrosis factor-α and activation of nuclear factor-κB by LPS. Collectively, these results suggest that OA has anti-inflammatory effects by inhibiting hyperpermeability, the expression of CAMs, and the adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapeutic agent for vascular inflammatory diseases.

Antiplatelet, anticoagulant, and profibrinolytic activities of baicalin

Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to possess anti-inflammatory and anti-viral activities. However, antiplatelet, anticoagulant, and profibrinolytic properties of baicalin have not been studied. In this study, the anticoagulant and antiplatelet activities of baicalin were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), the activities of cell-based thrombin and activated factor X (FXa), platelet aggregation and thrombus formation. The effects of baicalin on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Our data showed that baicalin inhibited thrombin-catalyzed fibrin polymerization and platelet functions, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. Baicalin also prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by baicalin. Collectively, these results indicate that baicalin possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents.

Inhibitory effects of lycopene on HMGB1-mediated pro-inflammatory responses in both cellular and animal models

High mobility group box 1 (HMGB1) mediates proinflammatory responses in inflammatory diseases. Lycopene found in tomatoes and tomato products has anti-oxidant, anti-cancer and antiinflammatory effects. The potential anti-inflammatory roles of lycopene in HMGB1-mediated proinflammatory responses in both primary human umbilical vein endothelial cells (HUVECs) and animal were investigated. The anti-inflammatory effects of lycopene were determined including permeability, monocyte adhesion and migration, and activation of proinflammatory proteins and HMGB1 receptors on HMGB1 activated HUVECs. In the in vivo model, the anti-inflammatory effect of lycopene was assessed by monitoring vascular permeability and migration of leukocytes to the peritoneal cavity of mice injected with lycopene. Lycopene inhibited lipopolysaccharide (LPS)-mediated release of HMGB1, expression of HMGB1-mediated tumor necrosis factor (TNF)-secretory phospholipase A2 (sPLA2)-IIA, and HMGB1-mediated pro-inflammatory signaling responses in endothelial cells. It did this through down-regulation of cell surface expression of cell adhesion molecules (CAMs), HMGB1 receptors, toll-like receptor (TLR)-2, and -4, and receptors for advanced glycation end products (RAGE). These findings suggest that lycopene promotes barrier integrity, inhibits monocyte adhesion and migration to HMGB1 activating HUVECs by blocking activation of proinflammatory cytokines and expression of CAMs and HMGB1 receptors, thereby showing its usefulness as a therapy for vascular inflammatory diseases.