Human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs) are capable of differentiating into several lineages and possess immunomodulatory properties. In this study, we investigated the soluble factor-mediated immunomodulatory effects of hAM-MSCs. Mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation was suppressed by hAM-MSCs in a dose-dependent manner as well as hAM-MSC culture supernatant. Moreover, interferon-gamma and interleukin (IL)-17 production significantly decreased from PBMC, whereas IL-10 from PBMCs and transforming growth factor beta (TGF-beta) production from hAM-MSCs significantly increased in co-cultures of hAM-MSCs and PBMCs. Production of several MSC factors, including hepatocyte growth factor (HGF), TGF-beta, prostaglandin E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in hAM-MSCs co-cultured with PBMCs. These results indicate that the immunomodulatory effects of hAM-MSCs may be associated with soluble factors (TGF-beta, HGF, PGE2, and IDO), suggesting that hAM-MSCs may have potential clinical use in regenerative medicine.
Amnion/cytology/*immunology ; Cell Differentiation/immunology ; Coculture Techniques ; Dinoprostone/genetics/immunology ; Female ; Hepatocyte Growth Factor/genetics/immunology ; Humans ; Immunologic Factors/*immunology ; Immunophenotyping ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/immunology ; Interferon-gamma/immunology ; Interleukin-10/analysis/immunology ; Interleukin-17/analysis/immunology ; Leukocytes, Mononuclear/cytology/immunology ; Mesenchymal Stem Cells/cytology/*immunology ; Pregnancy ; RNA, Messenger/chemistry/genetics ; Regenerative Medicine/methods ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta/genetics/immunology

The anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG) were investigated in vitro and in vivo using croton oil-induced inflammation models. Croton oil (20 microgram/mL) up-regulated mRNA expression of cyclooxygenase (COX)-I and COX-II in the macrophage cell line, RAW 264.7, resulting in the release of high concentrations of prostaglandin E2 (PGE2). EAG (1~10 microgram/mL) markedly suppressed croton oil-induced COX-II mRNA expression and PGE2 production. Application of croton oil (5% in acetone) to mouse ears caused severe local erythema, edema and vascular leakage, which were significantly attenuated by oral pre-treatment with EAG (50~500 mg/kg). Croton oil dramatically increased blood levels of interleukin (IL)-6 and PGE2 without affecting tumor-necrosis factor (TNF)-alpha and nitric oxide (NO) levels. EAG pre-treatment remarkably lowered IL-6 and PGE2, but did not alter TNF-alpha or NO concentrations. These results indicate that EAG attenuates inflammatory responses in part by blocking the COX-PGE2 pathway. Therefore, EAG could be a promising candidate for the treatment of inflammatory diseases.
Angelica/*immunology ; Animals ; Cell Line ; Cyclooxygenase 1/genetics/*immunology ; Cyclooxygenase 2/genetics/*immunology ; Dinoprostone/genetics/immunology ; Inflammation/drug therapy/enzymology/*immunology ; Interleukin-6/blood ; Macrophages ; Male ; Mice ; Mice, Inbred ICR ; Nitric Oxide/blood ; Phytotherapy/*methods ; Plant Extracts/*pharmacology/therapeutic use ; Plant Roots/immunology ; RNA, Messenger/chemistry/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha/blood

Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor (GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (P38MAPK) and activator protein-1 (AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.
Aesculus ; chemistry ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; Dinoprostone ; immunology ; Edema ; drug therapy ; genetics ; immunology ; Escin ; administration & dosage ; Female ; Humans ; Interleukin-1beta ; genetics ; immunology ; Male ; Mice ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology

Inflammation is closely related to the progression of cancer as well as tumorigenesis. Here, we investigated the effect of prostaglandin E2 (PGE2) and interleukin-1beta (IL-1beta) on E-cadherin expression in SNU719 gastric cancer cells. E-cadherin expression decreased as the dose or exposure time of PGE2 and IL-1beta increased, whereas Snail expression increased with dose or time of PGE2 and IL-1beta. E-cadherin expression reduced by PGE2 treatment increased after the transfection of Snail siRNA. Neutralization of IL-1beta using anti-IL-1beta antibody blocked the expression pattern of E-cadherin and Snail occurred by IL-1beta treatment. However, there was no synergic effect of IL-1beta and PGE2 on the expression pattern of E-cadherin and Snail. In conclusion, inflammatory mediators reduced E-cadherin expression by enhancing Snail expression in gastric cancer cells. Inflammation-induced transcriptional regulation of E-cadherin in gastric cancer has implications for targeted chemoprevention and therapy.
Antibodies/immunology ; Antineoplastic Agents/pharmacology ; Cadherins/*metabolism ; Cell Line, Tumor ; Dinoprostone/*pharmacology ; Gene Expression Regulation/*drug effects ; Humans ; Interleukin-1beta/immunology/*pharmacology ; RNA Interference ; RNA, Small Interfering/metabolism ; Stomach Neoplasms/metabolism/pathology ; Transcription Factors/antagonists & inhibitors/genetics/*metabolism

Animals ; Carbon Tetrachloride ; toxicity ; Dinoprostone ; blood ; Ginsenosides ; pharmacology ; therapeutic use ; Liver ; ultrastructure ; Liver Cirrhosis, Experimental ; drug therapy ; enzymology ; immunology ; Male ; Panax ; Phospholipases A ; biosynthesis ; genetics ; Phospholipases A2 ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; biosynthesis

Triptolide (TPT), an active compound extracted from Chinese herb Tripterygium wilfordii , has been used in therapy of rheumatoid arthritis (RA). In this study, after synovial fibroblasts from rheumatoid arthritis (RASFs) were treated with TPT, we investigated its effect on the differentiation of Th17 cells. Firstly, the mRNA level of cyclooxygenase (COX) wad detected by qRT-PCR and the protein level of prostaglandin E2 (PGE2) was tested by ELISA in RASFs treated with different concentrations (0, 10, 50, 100 nmol L-1 ) of TPT. Then after TPT pre-treated RASFs and RA CD4 + T cells wer e co-cultured for 3 days in the presence or absence of PGE2, IL-17 and IFN-gamma production in CD4 T cell subsets were detected by flow cytometry. The results showed TPT decreased the mRNA experssion of COX2 and the secretion of PGE2 in RASFs in a dose-dependent manner(P <0. 05). We further found that differentiation of Thl7 cells was downregulated in a dose-dependent manner, and exogenous PGE2 could reverse the inhibition of Th17 cell differentiation(P <0. 05). Taken together, our results demonstrated that TPT inhibited the mRNA level of COX2 and the secretion of PGE2 in RASFs, which partly led to impaired Th17 cell differentiation in vitro.
Arthritis, Rheumatoid ; drug therapy ; enzymology ; immunology ; Cell Differentiation ; drug effects ; Cell Line ; Cyclooxygenase 2 ; genetics ; metabolism ; Dinoprostone ; metabolism ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Fibroblasts ; drug effects ; immunology ; Gene Expression Regulation, Enzymologic ; drug effects ; Humans ; Middle Aged ; Phenanthrenes ; pharmacology ; Synovial Fluid ; drug effects ; Th17 Cells ; drug effects ; pathology