Bone marrow cells repair cigarette smoke-induced emphysema in rats.

The therapeutic potential of stem cells in chronic obstructive pulmonary disease is not well known although stem cell therapy is effective in models of other pulmonary diseases. We tested the capacities of bone marrow cells (BMCs), mesenchymal stem cells (MSCs), and conditioned media of MSCs (MSC-CM) to repair cigarette smoke-induced emphysema. Inbred female Lewis rats were exposed to cigarette smoke for 6 mo and then received BMCs, MSCs, or MSC-CM from male Lewis rats. For 2 mo after injection, the BMC treatment gradually alleviated the cigarette smoke-induced emphysema and restored the increased mean linear intercept. The BMC treatment significantly increased cell proliferation and the number of small pulmonary vessels, reduced apoptotic cell death, attenuated the mean pulmonary arterial pressure, and inhibited muscularization in small pulmonary vessels. However, only a few male donor cells were detected from 1 day to 1 mo after BMC administration. The MSCs and cell-free MSC-CM also induced the repair of emphysema and increased the number of small pulmonary vessels. Our data show that BMC, MSCs, and MSC-CM treatment repaired cigarette smoke-induced emphysema. The repair activity of these treatments is consistent with a paracrine effect rather than stem cell engraftment because most of the donor cells disappeared and because cell-free MSC-CM also induced the repair.

Regulation of expression of matrix metalloproteinase-9 by JNK in Raw 264.7 cells: presence of inhibitory factor(s) suppressing MMP-9 induction in serum and conditioned media.

Matrix metalloproteinase-9 (MMP-9) secreted from macrophages plays an important role in tissue destruction and inflammation through degradation of matrix proteins and proteolytic activation of cytokines/chemokines. Whereas the MEK-ERK and PI3K- Akt pathways up-regulate MMP-9 expression, regulation of MMP-9 by JNK remains controversial. Presently, we aimed to determine the role of JNK in MMP-9 regulation in Raw 264.7 cells. Inhibition of JNK by the JNK inhibitor SP600125 induced MMP-9 in the absence of serum and suppressed the expression of TNF-alpha, IL-6 and cyclooxygenase-2 in LPS-treated Raw 264.7 cells. In a knockdown experiment with small interfering RNA, suppression of JNK1 induced MMP-9 expression. Interestingly, mouse serum suppressed SP600125- mediated MMP-9 induction, similar to IFN-gamma. However, the inhibitory activity of mouse serum was not affected by pyridone 6, which inhibits Janus kinase downstream to IFN-gamma. In addition to mouse serum, conditioned media of Raw 264.7 cells contained the inhibitory factor(s) larger than 10 kDa, which suppressed SP600125- or LPS-induced MMP-9 expression. Taken together, these data suggest that JNK1 suppresses MMP-9 expression in the absence of serum. In addition, the inhibitory factor(s) present in serum or secreted from macrophages may negatively control MMP-9 expression.

Inhibitory effect of chitooligosaccharides on matrix metalloproteinase-9 in human fibrosarcoma cells (HT1080).

Matrix metalloproteinase-9 (MMP-9) has gelatinase activity and plays an important role in cancer invasion and metastasis. Therefore, inhibition of specific types of MMPs including MMP-9 has become an attractive target for therapeutic intervention. The aim of this study was to investigate the effect of chitooligosaccharides (COS) on activity and expression of MMP-9 in HT1080 cells. The inhibitory effect of COS with different molecular masses was examined by gelatin zymography, reverse transcriptase-polymerase chain reaction (RT-PCR), gene reporter assay, and Western blot analysis. MMP-9 inhibition in the presence of COS was clearly observed in gelatin zymography. Specifically, 1- to 3-kDa COS (COS-I) exhibited the highest inhibitory effect on MMP-9 activity in HT1080 cells among tested molecular mass fractions. It was also found that COS-I was capable of inhibiting both gene and protein expression of MMP-9 (P<0.01). These results suggest that low molecular mass COS can be considered as a potent inhibitor of MMP-9.

Physcion from marine-derived fungus Microsporum sp. induces apoptosis in human cervical carcinoma HeLa cells.

Recently, the relationship between apoptosis and cancer has been emphasized and the induction of apoptosis is recognized as one of the key mechanisms of anti-cancer agents. Marine-derived fungi are valuable sources of structurally diverse bioactive anticancer agents. In the present study, a marine-derived fungus, Microsporum sp. was cultured and an anthraquinone derivative, physcion (11.8 mg) was isolated from the culture broth extract (1710 mg). Physcion has shown cytotoxic effect on human cervical carcinoma HeLa cells and its apoptosis induction in HeLa cells was investigated by the expressions of p53, p21, Bax, Bcl-2, caspase-9, and caspase-3 proteins. The Western blot analysis has revealed that physcion could significantly induce cell apoptosis through down-regulating of Bcl-2 expression, up-regulating of Bax expression, and activating the caspase-3 pathway. Furthermore, physcion induced the formation of reactive oxygen species (ROS) in HeLa cells. Collectively, these results suggest that physcion could be a potential candidate in the field of anticancer drug discovery against human cervical cancer.

Bioactive sterols from marine resources and their potential benefits for human health.

Bioactive agents from marine resources have shown their valuable health beneficial effects. Therefore, increase knowledge on novel functional ingredients with biological activities from marine animal and microbe has gained much attention. Sterols are recognized as potential in development functional food ingredients and pharmaceutical agents. Marine resources, with a great diversity, can be a very interesting natural resource of sterols. This chapter focuses on biological activities of marine animal and microbe sterols with potential health beneficial applications in functional foods and pharmaceuticals.