Activation of multiple proteolysis systems contributes to acute cadmium cytotoxicity.

Cadmium exhibits both toxic and carcinogenic effects, and its cytotoxicity is linked to various cellular pathways, such as oxidative stress, ubiquitin-proteasome, and p53-mediated response pathways. The molecular mechanism(s) underlying cadmium cytotoxicity appears to be complex, but remains largely unclear. Here, we examined the effects of cadmium on the protein catabolism using two surrogate markers, DNA topoisomerases I and II alpha and its contribution to cytotoxicity.

DNA topoisomerase III alpha regulates p53-mediated tumor suppression.

Purpose: Human DNA topoisomerase III alpha (hTOP3α) is involved in DNA repair surveillance and cell-cycle checkpoints possibly through formatting complex with tumor suppressors. However, its role in cancer development remained unsolved.

Experimental Design: Coimmunoprecipitation, sucrose gradient, chromatin immunoprecipitation (ChIP), real time PCR, and immunoblotting analyses were performed to determine interactions of hTOP3α with p53.

A negative feedback of the HIF-1α pathway via interferon-stimulated gene 15 and ISGylation.

Purpose: The IFN-stimulated gene 15 (ISG15)- and ubiquitin-conjugation pathways play roles in mediating hypoxic and inflammatory responses. To identify interaction(s) between these two tumor microenvironments, we investigated the effect of ISG15 on the activity of the master hypoxic transcription factor HIF-1α.

Experimental Design: IFN and desferoxamine treatments were used to induce the expression of ISGs and HIF-1α, respectively.

Anthracenedione-methionine conjugates are novel topoisomerase II-targeting anticancer agents with favorable drug resistance profiles.

Structure-associated drug resistance and DNA-unwinding abilities have greatly limited the clinical usage of anthracenediones, including mitoxantrone (MX) and ametantrone (AT), which intercalate into DNA and induce topoisomerase II (TOP2)-mediated DNA break. We studied a series of 1,4-bis(2-amino-ethylamino) MX- and AT-amino acid conjugates (M/AACs) and showed that abilities in cancer cell killing correlate with the amounts of chromosomal DNA breaks induced by M/AACs. Notably, the 1,4-bis-L/l-methionine-conjugated MAC (L/LMet-MAC) exhibits DNA-breaking, cancer cell-killing and anti-tumor activities rivaling those of MX.

Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis.

Objective: The pathogenesis of rheumatoid arthritis (RA) reflects an ongoing imbalance between proinflammatory and antiinflammatory cytokines. Interleukin-20 (IL-20) has proinflammatory properties for keratinocytes. In this study, we sought to determine whether IL-20 is involved in RA.

IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice.

Objective: Atherosclerosis is a chronic inflammatory disease with immune cell infiltration. Various cytokines and chemokines have been characterized as pro- or antiatherogenic factors. Interleukin-20 (IL-20) belongs to the IL-10 family and is a proinflammatory cytokine involved in the pathogenesis of psoriasis.

Induction of interleukin-19 and interleukin-22 after cardiac surgery with cardiopulmonary bypass.

Background: Interleukin (IL)-19, IL-20, and IL-22, three novel cytokines in the IL-10 family, have recently been discovered. The biological functions and clinical implications of these cytokines are not clear. We aimed to analyze if serum levels of these cytokines were altered in inflammatory responses of postoperative cardiopulmonary bypass (CPB) and investigate the molecular mechanism involved in cytokine induction.

IL-20: biological functions and clinical implications.

IL-20 belongs to the IL-10 family and plays a role in skin inflammation and the development of hematopoietic cells. Little is known about its other biological functions and clinical implications, however. Updated information about IL-20, such as its identification, expression, receptors, signaling, biological activities, and potential clinical implications, is illustrated in this review based on our research and on data available in the literature.