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P11, a novel peptide ligand containing a PDZ-binding motif (Ser-Asp-Val) with high affinity to integrin ␣ v ␤ 3 was identified from a hexapeptide library (PS-SPCL) using a protein microarray chip-based screening system. Here, we investigated the inhibitory mechanism of P11 (HSD-VHK) on tumor-induced angiogenesis via a pharmacoproteomic approach. P11 was rapidly internalized by , human umbilical vein endothelial cells (HUVECs) via an integrin ␣ v ␤ 3 -mediated event. Caveolin and clathrin appeared to be involved in the P11 uptake process. The cell-penetrating P11 resulted in suppression of bFGF-induced HUVEC proliferation in a dose-dependent manner. Phosphorylation of extracellular-signal regulated kinase (ERK1/2) and mitogen-activated protein kinase kinase (MEK) in bFGFstimulated HUVECs was inhibited by cell-permeable P11. Proteomic analysis via antibody microarray showed upregulation of p53 in P11-treated HUVECs, resulting in induction of apoptosis via activation of caspases-3, -8, and -9. Several lines of experimental evidence strongly suggest that the molecular mechanism of P11, a novel antiangiogenic agent, inhibits bFGF-induced HUVEC proliferation via mitogen-activated protein kinase kinase and extracellular-signal regulated kinase inhibition as well as p53-mediated apoptosis related with activation of

We investigated the anti-angiogenic effects of the water extract of HangAmDan (WEHAD), which is a crude extract of nine Korean medicinal substances of animal and plant origin. In human umbilical vein endothelial cells, WEHAD significantly inhibited bFGF-induced proliferation, adhesion, migration, and capillary tube formation. We used an antibody array to perform an analysis of signaling proteins, which showed up-regulated expression of various proteins including RAD51, RAD52, and p73, and down-regulated expression of pFAK. Blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD was markedly reduced in length compared with a PBS-treated control group. These results suggest that inhibition of angiogenesis by WEHAD may be the mechanism of action for the anti-cancer effects of HAD.angiogenesis, HangAmDan, WEHAD, antibody array, HUVEC Citation:

Background Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the anti‐asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation. Methods Six‐week‐old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A. lwoffii during the sensitization period. Airway hyperresponsiveness and inflammation were evaluated. Using flow cytometry, macrophages were subclassified according to their activation status. In the in vitro study, a murine alveolar macrophage cell line (MH‐S) treated with or without A. lwoffii before IL‐13 stimulation were analysed by quantitative RT‐PCR. Results In a murine asthma model, the number of inflammatory cells, including macrophages and eosinophils, decreased in mice treated with A. lwoffii (A. lwoffii/OVA group) compared with untreated mice (OVA group). The enhanced expression of MHCII in macrophages in the OVA group was decreased by A. lwoffii treatment. M2 macrophage subtypes were significantly altered. A. lwoffii treatment decreased CD11b+M2a and CD11b+M2c macrophages, which showed strong positive correlations with Th2 cells, ILC2 and eosinophils. In contrast, CD11b+M2b macrophages were significantly increased by A. lwoffii treatment and showed strong positive correlations with ILC1 and ILC3. In vitro, A. lwoffii down‐regulated the expression of M2 markers related but up‐regulated those related to M2b macrophages. Conclusions and Clinical Relevance Intranasal A. lwoffii exposure suppresses asthma development by suppressing the type 2 response via modulating lung macrophage activation, shifting M2a and M2c macrophages to M2b macrophages.

The inhibitory effects of the water extract of HangAmDan-B (WEHAD-B), which is a crude extract of eight Korean medicinal animals and plants on bFGF-induced neovascularization were investigated. WEHAD-B significantly prevented bFGF-induced HUVE cell proliferation, adhesion, migration, and capillary-like tubular network formation. Half-maximal inhibition of proliferation on the endothelial cells by WEHAD-B was observed at a concentration of approximately 250 μg/mL. Our antibody microarray-based ProteoChip data showed that WEHAD-B increased the expression of STAT1 and Rb2, which are involved in cell growth, apoptosis, and controlling the cell cycle in bFGF-induced HUVECs. These results indicate that the inhibition of bFGF-induced angiogenesis by WEHAD-B may be due to upregulation of cell signaling proteins, STAT1 and Rb2. The blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD-B was markedly reduced in length compared with a PBS-treated control group. Taken together, these data suggest that antibody-arrayed ProteoChip technology may be an useful tool for determining molecular mechanism of natural products in biological samples.

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