The suppressive effect of tamarixetin, isolated from Inula japonica, on degranulation and eicosanoid production in bone marrow-derived mast cells.

BACKGROUND: The study aimed to evaluate the inhibitory effect of tamarixetin on the production of inflammatory mediators in immunoglobulin E /antigen-induced mouse bone marrow-derived mast cells (BMMCs). MATERIAL AND METHODS: Tamarixetin isolated from Inula japonica was infected into BMMCs. The inhibitory effect of tamarixetin were analyzed by quantifying ß-hexosaminidase, eicosanoid generation, intracellular calcium measurement, and Western blot analysis. RESULTS: Tamarixetin effectively decreased degranulation and the eicosanoid generation such as leukotriene C4 and prostaglandin D2 in BMMCs. To elucidate the mechanism involved, we investigated the effect of tamarixetin on the phosphorylation of signal molecules. Tamarixetin inhibited the phosphorylation of protein kinase B (Akt) and its downstream signal molecules including IκB kinase and nuclear factor-κB. Besides, tamarixetin downregulated the phosphorylation of cytosolic phospholipase A2 and p38 mitogen-activated protein kinase.Conclusion: In summary, tamarixetin inhibits degranulation and eicosanoid generation through the phospholipase Cγ1 as well as Akt pathways. It could be potential for the prevention of allergic inflammatory diseases in BMMCs.

Probability of causation for occupational cancer after exposure to ionizing radiation

BACKGROUND: Probability of causation (PC) is a reasonable way to estimate causal relationships in radiation-related cancer. This study reviewed the international trend, usage, and critiques of the PC method. Because it has been used in Korea, it is important to check the present status and estimation of PC in radiation-related cancers in Korea. METHODS: Research articles and official reports regarding PC of radiation-related cancer and published from the 1980s onwards were reviewed, including studies used for the revision of the Korean PC program. PC has been calculated for compensation-related cases in Korea since 2005. RESULTS: The United States National Institutes of Health first estimated the PC in 1985. Among the 106 occupational diseases listed in the International Labor Organization Recommendation 194 (International Labor Office (ILO), ILO List of Occupational Diseases, 2010), PC is available only for occupational cancer after ionizing radiation exposure. The United States and United Kingdom use PC as specific criteria for decisions on the compensability of workers’ radiation-related health effects. In Korea, PC was developed firstly as Korean Radiation Risk and Assigned Share (KORRAS) in 1999. In 2015, the Occupational Safety and Health Research Institute and Radiation Health Research Institute jointly developed a more revised PC program, Occupational Safety and Health-PC (OSH-PC). Between 2005 and 2015, PC was applied in 16 claims of workers’ compensation for radiation-related cancers. In most of the cases, compensation was given when the PC was more than 50%. However, in one case, lower than 50% PC was accepted considering the possibility of underestimation of the cumulative exposure dose. CONCLUSIONS: PC is one of the most advanced tools for estimating the causation of occupational cancer. PC has been adjusted for baseline cancer incidence in Korean workers, and for uncertainties using a statistical method. Because the fundamental reason for under- or over-estimation is probably inaccurate dose reconstruction, a proper guideline is necessary.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cgamma1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-kappaB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.