Mast cell-mediated allergic response is suppressed by Sophorae flos: inhibition of SRC-family kinase.

Complementary and alternative medicines are considered as a promising direction for the development of anti-allergic therapies in oriental countries. We screened approximately 100 oriental herbal medicines for anti-allergic activity. Sophorae flos exhibited the most potent effect on degranulation in antigen-stimulated mast cells. We further investigated the effect of Sophorae flos on the IgE-mediated allergic response in vivo and its mechanism of action in mast cells. Sophorae flos exhibited a significant inhibitory effect on degranulation in antigen-stimulated mast cells with IC(50) values of approximately 31.6 microg/mL (RBL-2H3 mast cells) and approximately 47.8 microg/mL (bone marrow-derived mast cells). Sophorae flos also suppressed the expression and secretion of TNF-alpha and IL-4 in the cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Sophorae flos inhibited the activating phosphorylation of Syk and LAT in mast cells. Further downstream, activating phosphorylation of Akt and the prototypic MAP kinases, namely, p38, ERK1/2, and JNK, were also inhibited. These results suggest that Sophorae flos inhibits the Src family kinase-dependent signaling cascades in mast cells and may thus exert anti-allergic activity.

Polygoni cuspidati radix inhibits the activation of Syk kinase in mast cells for antiallergic activity.

The antiallergic activity of Polygoni cuspidati radix (PR) and the mechanism of action by which it functions were investigated in this study. The extract of PR exhibited potent inhibitory activity in mast cells; its IC50 values were 62 +/- 2.1 microg/ml for RBL-2H3 mast cells and 46 +/- 3.2 microg/m for bone marrow-derived mast cells by antigen stimulation, and it also suppressed the expression of tumor necrosis factor-alpha and interleukin-4 in RBL-2H3 cells. According to the in vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis, in a dose-dependent manner. With regard to its mechanism of action, PR inhibited the activating phosphorylation of Syk, a key signaling protein for the activation of mast cells. It also suppressed Akt and the mitogen-activated protein kinases ERK1/2, p38, and JNK, which are critical for the production of various inflammatory cytokines in mast cells. The results of the study indicate that the antiallergic activity of PR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk activating phosphorylation in mast cells.

Role of Th1 and Th17 cells in the development and complexity of coronary artery disease: comparison analysis by the methods of flow cytometry and SYNTAX score.

BACKGROUND: There have been few reports on the relationship between the expression of the CD4⁺ T cells producing interferon-γ (Th1)/interleukin-17 (Th17) and degree of atherosclerosis. Thus, we analyzed Th1 and Th17 cell frequencies in patients with noncardiac chest pain (control), stable angina (SA), and acute myocardial infarction (AMI), and compared the complexity of the coronary artery with the SYNTAX score. PATIENTS AND METHODS: This study included 124 patients with a complaint of chest pain who underwent coronary angiography (control: 30 patients, SA: 47 patients, AMI: 47 patients). Peripheral blood was sampled during coronary angiography. Mononuclear cells from patients were stimulated for 4 h ex vivo. After staining with specific antibodies and fluorescence, the frequencies of Th1 and Th17 cells were measured by flow cytometry. The SYNTAX score was calculated by coronary angiography and a web-based calculator. RESULTS: There was no significant difference in the baseline characteristics, except the higher frequencies of hypertension in SA patients (76.1%) and smoking in AMI patients (53.3%). Patients with SA showed a significantly higher frequency of Th1 cells (21.56±9.57%) compared with controls (14.84±8.58%) and patients with AMI (9.04±7.02%) (P<0.001). The frequency of Th17 cells also increased in SA patients (control: 1.90±1.05%, SA: 2.96±1.42%, AMI: 1.32±0.92%, P<0.001). The SYNTAX score was significantly higher in SA patients (SA: 21.51±11.67, AMI: 15.36±8.84, P=0.006) and correlated with the frequencies of Th1 and Th17 cells (r=0.359, P=0.001; r=0.248, P=0.031; respectively). CONCLUSION: Th1 and Th17 cells were related to the development of SA, but not AMI. They could be a useful marker for the complexity of atherosclerosis in coronary artery disease.

Morus bombycis extract suppresses mast cell activation and IgE-mediated allergic reaction in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus bombycis Koidzumi (MB) is widely distributed throughout Korea, where it is used as a traditional folk remedy for the treatment of allergic diseases including asthma. However, the pharmacological effect and the mechanistic study of MB have not been investigated. We aimed to investigate the anti-allergic activity of MB in vitro and in vivo and the mechanism of its action on mast cells. MATERIALS AND METHODS: The anti-allergic activity of MB extract (MBE) was assessed using passive cutaneous anaphylaxis (PCA) in mice and mouse bone marrow-derived mast cells (BMMCs) in vitro. The effects of MBE on mast cell activation were evaluated by using the ß-hexosaminidase release assay, reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting analysis. RESULTS: MBE reversibly inhibited degranulation and generation of cytokines (TNF-α and IL-4) in antigen-stimulated mast cells. With regard to its mechanism of action, MBE inhibited the activation of Lyn and Syk, which have essential roles in degranulation and the production of various inflammatory cytokines. MBE also inhibited the activating phosphorylation of mitogen-activated protein (MAP) kinases, Erk1/2, p38, JNK, and Akt. In agreement with its in vitro effect, MBE significantly inhibited mast cell-mediated PCA reactions in IgE-sensitized mice. CONCLUSIONS: The present results strongly suggest that MBE exerts an anti-allergic effect, both in vitro and in vivo by inhibiting the Lyn and Syk pathways in mast cells. Therefore, MBE may be useful for the treatment of allergic diseases, including atopic dermatitis and allergic asthma.

Application of radiographic images in diagnosis and treatment of deep neck infections with necrotizing fasciitis: a case report.

The advent and wide use of antibiotics have decreased the incidence of deep neck infection. When a deep neck infection does occur, however, it can be the cause of significant morbidity and death, resulting in airway obstruction, mediastinitis, pericarditis, epidural abscesses, and major vessel erosion. In our clinic, a patient with diffuse chronic osteomyelitis of mandible and fascial space abscess and necrotic fasciitis due to odontogenic infection at the time of first visit came. We successfully treated the patient by early diagnosis using contrast-enhanced CT and follow up dressing through the appropriate use of radiographic images.

Tumor necrosis factor alpha-induced interleukin-32 is positively regulated via the Syk/protein kinase Cdelta/JNK pathway in rheumatoid synovial fibroblasts.

OBJECTIVE: Interleukin-32 (IL-32) is a recently discovered cytokine that appears to play a critical role in human rheumatoid arthritis (RA). It is highly expressed in synovium and fibroblast-like synoviocytes (FLS) from RA patients, but not in patients with osteoarthritis (OA). This study was undertaken to assess IL-32 levels in RA synovial fluid (SF) and to investigate the secretion and regulation of IL-32 in RA FLS. METHODS: FLS and SF were obtained from the joints of RA patients. The secretion and expression of IL-32 and activation of signaling molecules were examined by enzyme-linked immunosorbent assay, immunoblotting, immunoprecipitation, reverse transcriptase-polymerase chain reaction, and small interfering RNA (siRNA) transfection. RESULTS: IL-32 levels were high in RA SF compared with OA SF. Furthermore, RA FLS expressed and secreted IL-32 when stimulated with tumor necrosis factor alpha (TNFalpha). TNFalpha-induced expression of IL-32 was significantly suppressed, in a dose-dependent manner, by inhibitors of Syk, protein kinase Cdelta (PKCdelta), and JNK and by knockdown of these kinases and c-Jun with siRNA. We also observed that PKCdelta mediated the activation of JNK and c-Jun, and experiments using specific inhibitors and siRNA demonstrated that Syk was the upstream kinase for the activation of PKCdelta. CONCLUSION: The present findings suggest that IL-32 may be a newly identified prognostic biomarker in RA, thereby adding valuable knowledge to the understanding of this disease. The results also demonstrate that the production of IL-32 in RA FLS is regulated by Syk/PKCdelta-mediated signaling events.