Sung-Kee Jo

Preventative effect of an herbal preparation (HemoHIM) on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4+ T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4+ T cells displayed increased Th1 (IFN-γ+ cell) as well as decreased Th2 (IL-4+ cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.

Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice

HemoHIM (a new herbal preparation of three edible herbs: Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by single injection of streptozotocin (STZ, 200 mg/kg, i.p.). In diabetic mice, HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the diabetic control group as well as elevated plasma insulin levels with preservation of insulin staining in pancreatic β-cells. HemoHIM treatment restored thymus weight, white blood cells, lymphocyte numbers, and splenic lymphocyte populations (CD4+ T and CD8+ T), which were reduced in diabetic mice, as well as IFN-γ production in response to Con A stimulation. These results indicate that HemoHIM may have potential as a glucose-lowering and immunomodulatory agent by enhancing the immune function of pancreatic β-cells in STZ-induced diabetic mice.

Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines.

The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines.

Protective Effects of HemoHIM on Immune and Hematopoietic Systems Against γ‐Irradiation

We examined the effect of HemoHIM on the protective efficacy of hematopoietic stem cells and on the recovery of immune cells against sublethal doses of ionizing radiation. Two‐month‐old mice were exposed to γ‐rays at a dose of 8, 6.5, or 5 Gy for a30‐day survival study, endogenous spleen colony formation, or other experiments, respectively. HemoHIM was injected intraperitoneally before and after irradiation. Our results showed that HemoHIM significantly decreased the mortality of sublethally irradiated mice. The HemoHIM administration decreased the apoptosis of bone marrow cells in irradiated mice. On the other hand, HemoHIM increased the formation of endogenous spleen colony in irradiated mice. In irradiated mice, the recovery of total leukocytes in the peripheral blood and lymphocytes in the spleen were enhanced significantly by HemoHIM. Moreover, the function of B cells, T cells, and NK cells regenerated in irradiated mice were significantly improved by the administration of HemoHIM. HemoHIM showed an ideal radioprotector for protecting hematopoietic stem cells and for accelerating the recovery of immune cells. We propose HemoHIM as a beneficial supplement drug during radiotherapy to alleviate adverse radiation‐induced effects for cancer patients. Copyright

Herbal preparation (HemoHIM) enhanced functional maturation of bone marrow-derived dendritic cells mediated toll-like receptor 4

BackgroundHemoHIM, which is an herbal preparation of three edible herbs (Angelicam gigas Nakai, Cnidium offinale Makino, and Peaonia japonica Miyabe), is known to have various biological and immunological activities, but the modulatory effects of this preparation on dendritic cells (DCs)-mediated immune responses have not been examined previously. DCs are a unique group of white blood cells that initiate primary immune responses by capturing, processing, and presenting antigens to T cells.ResultsIn the present study, we investigated the effect of HemoHIM on the functional and phenotypic maturation of murine bone marrow-derived dendritic cells (BMDCs) both in vitro and in vivo. The expression of co-stimulatory molecules (CD40, CD80, CD86, MHC I, and MHC II) and the production of cytokines (IL-1β, IL-6, IL-12p70, and TNF-α) were increased by HemoHIM in BMDCs. Furthermore, the antigen-uptake ability of BMDCs was decreased by HemoHIM, and the antigen-presenting ability of HemoHIM-treated mature BMDCs increased TLR4-dependent CD4+ and CD8+ T cell responses.ConclusionsOur findings demonstrated that HemoHIM induces TLR4-mediated BMDCs functional and phenotypic maturation through in vivo and in vitro. And our study showed the antigen-presenting ability that HemoHIM-treated mature BMDCs increase CD4+ and CD8+ T cell responses by in vitro. These results suggest that HemoHIM has the potential to mediate DC immune responses.

Inhibitory Effects of a Herbal Composition (HemoHIM) on the Activation of Human Mast Cell Line (HMC-1)

In our previous study, a novel herb mixture (HIM-Ⅰ) of Angelica gigas radix, Cnidium officinale rhizoma, and Paeonia japonica radix was developed to protect the intestinal and immune systems and to promote their recovery from radiation damage. A new herbal composition (HemoHIM) with the high immune modulating activity was developed from HIM-Ⅰ. In the present study, we examined the effects of HemoHIM on the maturation process of murine bone marrow (BM)-derived dendritic cells (DC). BM cells were cultured in the presence of IL-4 and GM-CSF and the generated immature DC were stimulated with HemoHIM for 24 hours. HemoHIM significantly enhanced the expression of co-stimulatory molecules, CD80 and CD86, especially. The activation capacity of HemoHIM-treated DC was significantly higher than that of immature DC, as analyzed by IL-2 and IFN-γ production and proliferation of the responding T cells in the co-culture with allogeneic T cells. The antigen-presenting capacity of HemoHIM-treated DC was also increased by the co-culture with OVA-specific T cells (HS-1), as analyzed by IL-2 and IFN-γ production and the proliferation. These results indicate that HemoHIM causes the maturation and activation of DC, which may be a part of mechanisms of immunomodulation by HemoHIM.

Inhibitory Effects of a New Herbal Composition (HemoHIM) on UVB-Induced Suppression of Langerhans Cell's Accessory Cell Function

In the previous results, we developed an effective products to apply as functional foods for overcome of radiation damage and reduction of side effects in radiotherapy. To verify the prevention of UVB-induced immunosuppression of immune cell function by HemoHIM, we studied on the mechanism of the skin immune function for the protection in UVB irradiation. In studies presented here, we showed that HemoHIM can prevent UVB-induced impairment of skin immune cell function by in vitro and in vivo assay. Exposure of freshly cultured murine dendritic cells (DCs) with IL-4/GM-CSF to UVB irradiation resulted in impairment of accessory function. This suppression could be prevented by addition of HemoHIM before or after to the cultures of UVB-irradiated DCs. We also tested the effects of HemoHIM on the suppression of contact hypersensitivity (CHS) treated oral or intraperitoneal administration. This UVB-suppressed CHS was prevented by administration of HemoHIM to UVB-irradiated mice. These results suggest that HemoHIM may prevent UVB-induced immune suppression in the skin.