Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.
Angelica ; Cell Culture Techniques ; Colitis ; Colitis, Ulcerative ; Colon ; Dextrans ; Interleukin-17 ; Medicine, Korean Traditional ; Neutrophils ; Plants ; Sodium ; T-Lymphocytes ; Th17 Cells ; Weight Loss

Gastric cancer is the second most common cause of cancer-related death in the world. A growing body of evidence indicates that inflammation is closely associated with the initiation, progression, and metastasis of many tumors, including those of gastric cancer. In addition, approximately 60% of the world's population is colonized by Helicobacter pylori, which accounts for more than 50% of gastric cancers. While the role of inflammation in intestinal and colonic cancers is relatively well defined, its role in stomach neoplasia is still unclear because of the limited access of pathogens to the acidic environment and the technical difficulties isolating and characterizing immune cells in the stomach, especially in animal models. In this review, we will provide recent updates addressing how inflammation is involved in gastric malignancies, and what immune characteristics regulate the pathogenesis of stomach cancer. Also, we will discuss potential therapeutics that target the immune system for the efficient treatment of gastric cancer.
Adaptive Immunity/*immunology ; B-Lymphocytes/immunology ; Cytokines/immunology ; Gastritis/immunology ; Helicobacter Infections/immunology ; Helicobacter pylori/immunology ; Humans ; Immunity, Innate/*immunology ; Immunotherapy/methods ; Receptors, Cytokine/immunology ; Stomach Neoplasms/diagnosis/*immunology/therapy ; T-Lymphocytes/immunology ; Tumor Microenvironment/*immunology

Kimura's disease is a rare chronic inflammatory disease of unknown etiology which appears primarily in young Asian males as non-tender subcutaneous swellings in the head and neck region. Histologic characteristics are the presence of lymphoid follicles, vascular proliferation and infiltration of eosinophils. Peripheral eosinophilia and elevated serum IgE are frequently combined. Systemic steroid therapy with surgical excision is the mainstay of treatment, though recurrence after surgery or discontinued steroid treatment is common. It has been known that about 16% of the cases are associated with renal diseases, particularly nephrotic syndrome. We present an 8-year-old boy with a past history of steroid-responsive, infrequently relapsing nephrotic syndrome who developed right buccal swelling and peripheral eosinophilia during the remission state. He has been managed with surgical resection, steroid and cyclosporine due to multiple recurrences.
Asian Continental Ancestry Group ; Child ; Cyclosporine ; Eosinophilia ; Eosinophils ; Head ; Humans ; Immunoglobulin E ; Male ; Neck ; Nephrotic Syndrome* ; Recurrence

A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.
Apoptosis ; Breast Neoplasms ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Cell Proliferation ; Cyclin D1* ; Cyclins* ; Estrogens ; G1 Phase ; Humans ; Phosphorylation* ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Retinoblastoma ; Signal Transduction ; Survival Rate ; Triple Negative Breast Neoplasms*

The authors request to correct the author name from Yoonho Lim to Yoongho Lim page 322.

Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam, is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of Itgam, knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrowderived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.

Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins. Furthermore, Gomisin G remarkably triggered the accumulation of cells at the sub-G1 phase which represents apoptotic cells. In addition, the level of cyclin D1 and phosphorylated retinoblastoma tumor suppressor protein (Rb) was also reduced by the treatment with Gomisin G thus curtailing cell cycle progression. These findings show the suppressive effect of Gomisin G by inhibiting proliferation and inducing apoptosis in LoVo cells. Taken together, these results suggest Gomisin G could be developed as a potential therapeutic compound against colon cancer.
Annexin A5 ; Apoptosis ; Caspase 3 ; Cell Cycle ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Cyclin D1 ; Phosphorylation ; Prognosis ; Retinoblastoma ; Ribose