Immune System Genes Show Links to Type 1 Diabetes – By Serena Gordon, HealthDay Reporter

WEDNESDAY, Sept. 8 (HealthDay News) — The exact cause of type 1 diabetes is still unknown, but international researchers have found a link between the blood sugar disorder and a network of immune system genes.

Using a genome-wide association study, the researchers found that a certain group of genes that react in response to viral infections were present in both rats and humans, and that those same genes were also associated with a susceptibility to type 1 diabetes.

“Diseases arise as a result of many genetic and environmental factors through gene networks that cause tissue damage,” explained study senior author Dr. Stuart Cook, the group head of molecular and cellular cardiology at the Medical Research Council Clinical Sciences Centre, and a professor of clinical and molecular cardiology at Imperial College in London.

“We used an approach to identify the major control points’ central command of an inflammatory gene network. This led us to uncover hundreds of new genes that might cause diabetes and one major control gene that controls the whole network,” said Cook.

He added that one of the genes belongs to a class of genes that might make a good target for drug therapy in the future.

Results of the study are published in the Sept. 9 issue of Nature.

Each year, more than 30,000 people are diagnosed with type 1 diabetes, formerly known as juvenile diabetes, according to the Juvenile Diabetes Research Foundation (JDRF). People with type 1 diabetes no longer produce enough of the hormone insulin to effectively use the sugars found in carbohydrate-containing foods. To survive, people with type 1 diabetes must take insulin injections or use an insulin pump for the rest of their lives.

Experts believe the disease is an autoimmune disease, which means that the body’s immune system mistakenly turns against healthy cells, such as the insulin-producing cells in the pancreas, and destroys them. People who develop type 1 diabetes are believed to have a genetic susceptibility to the disease that’s then triggered by something in the environment, possibly a virus.

In the current study, the researchers didn’t initially set out to look for type 1 diabetes genes. They started out by looking at a certain group of genes in rats, in this case a network of genes controlled by a gene called interferon regulatory factor 7 (IRF7). IRF7 is like a master switch that controls the genes in its network. The entire network of genes controlled by IRF7 is called the IRF7-driven inflammatory network (IDIN).

The researchers discovered that when there were differences in IRF7, there were also differences in the way other genes expressed themselves.

Cook and his colleagues then searched for a network of genes in humans that might behave the same way. They found an area on chromosome 13q32 that is controlled by a gene called the “Epstein-Barr virus induced gene 2” (Ebi2). This gene appeared to be the human equivalent of the IRF7 gene in rats.

Within this human version of the IDIN, research found a gene called IFIH1, which has been found in other research to be associated with the development of type 1 diabetes.

“Usually, research starts from the genetics and goes to function. Here, they started with a function — [an immune system reaction] — and were looking for a gene,” explained Marie Nierras, director of research and scientific affairs for the JDRF.

“The value of such a result is that if you can get to the same place using more than one pathway, it tends to support the hypothesis,” she said.

In this case, the hypothesis supported is the idea that type 1 diabetes may be triggered by an immune system response to a virus. However, Nierras stressed that this study doesn’t conclusively prove that a virus is the trigger for type 1 diabetes.

“We know better today that this network of genes is involved, and with a network, you have many targets you can test. This research invites us to plan experiments going forward, and opens up many more questions, like ‘If I disrupt this branch of the network, do I disrupt diabetes?’ Or, ‘If you look back at previous research knowing this study’s results, does that help to better explain previous results?'” said Nierras.

Cook said this type of genome-wide association study can be used for other diseases as well, and that his team is hoping to eventually develop a new drug based on the genetic target they discovered.

More information

Learn more about type 1 diabetes and its causes from the U.S. National Library of Medicine.

SOURCES: Stuart Cook, M.D., Ph.D., group head, molecular and cellular cardiology, the Medical Research Council Clinical Sciences Centre, and professor, clinical and molecular cardiology, Imperial College, London; Marie Nierras, Ph.D., director, research and scientific affairs, Juvenile Diabetes Research Foundation, New York City; Sept. 9, 2010, Nature

Copyright © 2010 HealthDay. All rights reserved.

Protein-bound polysaccharide-K (PSK) directly enhanced IgM production in the human B cell line BALL-1

Maruyama S, Akasaka T, Yamada K, Tachibana H.

Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka, Japan.


Protein-bound polysaccharide-K (PSK) prepared from the basidiomycete Coriolus versicolor has been used as a biological response modifier for the treatment of cancer patients. Many studies describing the immunomodulatory effects and direct anti-cancer effects of PSK have been reported. Most of studies describing the immunomodulatory effects focused on cellular immunity, although there were several studies which focused on humoral immunity where PSK was shown to be able to induce antibody production in vivo. However, even in these humoral immunity studies, it is thought that the enhancement of antibody production was due to the activation of cellular immunity. In this study, we investigated the direct effect of PSK on B cells and discovered that PSK was able to enhance IgM production in the human B cell line BALL-1. Furthermore, BALL-1 was shown to have the characteristic features of B-1a cells, which are independently involved in the primary immune response. These results show that there is a possibility that PSK directly acts on B cells and simultaneously enhances both humoral immunity and cellular immunity.

PMID: 18848763 [PubMed – indexed for MEDLINE]

Polysaccharopeptide mimics ciclosporin-mediated Th1/Th2 cytokine balance for suppression of activated human T cell proliferation by MAPKp38 and STAT5 pathways.

Lee CL, Sit WH, Jiang PP, So IW, Wan JM.

School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China.


The activation of T helper (Th) cell subsets plays an important role in the human immune system. Uncontrolled Th1 and Th2 responses lead to autoimmune and inflammatory diseases, respectively. The identification of agents that modulate the Th1/Th2 cytokines is therefore essential for controlling these diseases. We recently reported that polysaccharopeptide (PSP) from Coriolus versicolor exhibited ciclosporin-like activities to control aberrant T lymphocyte activation. Here, we compared the properties of PSP with ciclosporin on cell proliferation, CD25+ expression, secretion of Th1/Th2 cytokines and activation of mitogen-activated protein kinase (MAPK)p38 and signal transducers and activators of transcription 5 (STAT5) on T cells. The data show that PSP alone suppresses the proliferation of activated T cells. PSP exhibited similar and additive inhibitory effects to ciclosporin to suppress activated T cell proliferation, Th1 cytokines and reduce CD3+/CD25+ cell expression, but not Th2 cytokine expression, which helps the cytokine balance shift towards Th2 dominance. These suppressive actions of PSP involved the MAPKp38 and STAT5 pathways. These findings refine our understanding of the effects of PSP on T lymphocytes and its adjuvant properties with the immunosuppressant ciclosporin for possible control of autoimmune diseases.

PMID: 18957170 [PubMed – indexed for MEDLINE]

Protoplast fusion betweenLentinula edodes andCoriolus versicolor.

Kim C, Choi EC, Kim BK.

Department of Microbial Chemistry, College of Pharmacy, Seoul National University, 151-742, Seoul, Korea.


Protoplast fusion between isoleucine-, arginine- and thymidine-requiring auxotroph (lle, Arg, Thy) ofLentinula edodes and arginine-requiring auxotroph (Arg) of Coriolus versicolor has been achieved using 30% polyethylene glycol (M.W. 4000) in 10 mMCaCl(2)-glycine solution (pH 8.0). Fusion hybrids were selected in the 0.6 M sucrose supplemented minimal media on the basis of nutritional complementation with fusion frequency of 7.4×10(-6). The hybrids included both parental and non-parental types in colony morphology, growth rate and isozyme patterns. We succeeded inter-order protoplast fusion between the auxotrophs ofLentinula edodes and Coriolus versicolor overcoming the natural barriers of incompatibility. We examined the characteristics of the hybrids and clarified the fusion process using electron microscopy.

PMID: 18982488 [PubMed – in process]

Three-dimensional x-ray imaging and analysis of fungi on and in wood.

Van den Bulcke J, Boone M, Van Acker J, Van Hoorebeke L.

Laboratory of Wood Technology, Faculty of Bioscience Engineering, Ghent University, Gent, Belgium.


As wood is prone to fungal degradation, fundamental research is necessary to increase our knowledge aiming at product improvement. Several imaging modalities are capable of visualizing fungi, but the X-ray equipment presented in this article can envisage fungal mycelium in wood nondestructively in three dimensions with submicron resolution. Four types of wood subjected to the action of the white rot fungus Coriolus versicolor (Linnaeus) Quélet (CTB 863 A) were scanned using an X-ray-based approach. Comparison of wood volumes before and after fungal exposure, segmented manually or semiautomatically, showed the presence of the fungal mass on and in the wood samples and therefore demonstrated the usefulness of computed X-ray tomography for mycological and wood research. Further improvements to the experimental setup are necessary to resolve individual hyphae and enhance segmentation.

PMID: 19709462 [PubMed – indexed for MEDLINE]

Modifications of amino acids during ferulic acid-mediated, laccase-catalysed cross-linking of peptides.

Steffensen CL, Stensballe A, Kidmose U, Degn PE, Andersen ML, Nielsen JH.

Department of Food Science, Faculty of Agricultural Sciences, Aarhus University, Research Centre Foulum, Tjele, Denmark.


Mass spectral analysis demonstrated oligomerization of peptides that had been subjected to oxidation catalysed by Trametes (Coriolus) versicolor laccase. Peptide oligomerization occurred only when cysteines or tyrosines were present in the peptides. MS/MS confirmed the cross-linking in tyrosine-containing peptides to be located between tyrosine residues. Ferulic acid mediated oligomerization of cysteine-containing peptides, but prevented cross-linking of tyrosines when used in the same concentration as the peptides. This suggests an antioxidative effect of ferulic acid in relation to tyrosine oxidation, although incorporation of ferulic acid into peptide oligomers was found in some of the tyrosine-containing peptides. No other modifications to amino acid residues by laccase-catalysed oxidation were observed by mass spectroscopy. Thus, it is suggested that oxidative modifications of other amino acids observed in proteins oxidized by laccase are not major reaction products of laccase-catalysed oxidation.

PMID: 19905979 [PubMed – indexed for MEDLINE]

[Impact of exogenous paraquat on enzyme exudation and biochemical changes of lignin degradation fungi]

Zhao Y, Li J, Chen Y, Huang H, Yu Z.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, China.


To study the effect of exogenous oxygen, we added water solution of paraquat to 7 d cultures of Coriolus versicolor for the next 148 h. Enzyme exudation and biochemiscal process were investigated on the addition of paraquat. We found that compared with the control (without paraquat), the addition of 30 micromol/L paraquat stimulated the activity of manganese dependent peroxidase (MnP), lignin peroxidase (LiP), and laccases (Lac) 7, 2.5 and 1.3 times, respectively. Also, addition of paraquat enhanced activity of superoxide dismutase (SOD) and catalase (CAT) in the first 48 h. Impact of paraquat on ligninolytic enzymes was significant than that on antioxidant enzyme. Addition of paraquat enhanced phenolic compounds and formaldehyde of cultures too. And concentration of malondialdehyde was increased in the first 24 h. The results showed that addition of paraquat promoted oxidative stress, but the antioxidant systems of the fungal strain are sufficient to prevent mycelia from oxidative stress. As exogenous oxygen, paraquat might be a useful substrate in degradation of lignocellulose.

PMID: 19938450 [PubMed – in process]

Design of reaction conditions for the enhancement of microbial degradation of dyes in sequential cycles.

Sanghi R, Dixit A, Verma P, Puri S.

Facility for Ecological and Analytical Testing, 302, Southern Laboratories, Institute of Technology, Kanpur-20 8016, India.


The present study evaluated the potential of white-rot fungal strain Coriolus versicolor to decolorize five structurally different dyes in sequential batch reactors under optimized conditions. The experiments were run continuously for seven cycles of 8 d each. High decolorizing activity was observed even during the repeated reuse of the fungus, especially when the old medium was replaced with fresh medium after every cycle. Biodegradation was the dominating factor as the fungus was able to produce the enzyme laccase mainly, to mineralize synthetic dyes. The nutrients and composition of the medium played important roles in sustaining the decolorisation potential of the fungus. Corncob was found be an easy and cheap substitute for carbon source for the fungus. Glucose consumption by the fungus was in accordance to its decolorisation activity and chemical oxygen demand (COD) reduction.

Immunomodulatory effects of polysaccharopeptide (PSP) in human PBMC through regulation of TRAF6/TLR immunosignal-transduction pathways.

Li W, Liu M, Lai S, Xu C, Lu F, Xiao X, Bao Y.

Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.


Context: Polysaccharopeptide (PSP) was extracted from Coriolus versicolor, and has been proved to be a valuable adjuvant for the combination with chemotherapy or radiotherapy in the treatment of various cancers. Objective: To understand the mechanism of PSP on immunomodulation, we examined gene expression and cytokine secretion associated with immunosignal-transduction signaling in human peripheral blood mononuclear cells (PBMCs). Methods: cDNA microarray and cytokine antibody array were used to identify differential gene expression profiles and cytokines secretion of PBMCs in the presence or absence of PSP for 24 h. The expression of the key genes and proteins related to Toll-like receptor (TLR) signaling and its downstream pathway was determined by RT-PCR or Western blot. Results: Compared with the control group, PSP up-regulated 22 genes expression (such as IFN-gamma, CXCL10, TLR4, TLR5) in 117 genes associated with TLR signaling. Twenty-three of genes (e.g., TLR9, TLR10, SARM1, TOLLIP) related with TLR signaling pathway were down-regulated in PBMCs under PSP treatments. Five of cytokines (GCSF, GM-CSF, IL-1alpha, IL-6, IFN-gamma) were up-regulated more than 1.3 times by PSP. The mRNA levels of TRAM, TRIF, and TRAF6, which are the key molecules of TLR signaling pathway, were markedly increased (P < 0.05). Moreover, the protein level of TRAF6 was also markedly increased (P < 0.01). Conclusions: PSP-regulated gene expression and cytokine secretion related to TLR signaling pathway in human PBMCs. Especially, TRAM-TRIF-TRAF6 subsignaling pathway of TLR may be one of the key associated signaling pathways in the immunomodulation of PSP.

PMID: 20131955 [PubMed – as supplied by publisher]

Effect of nitrogen sources and vitamins on ligninolytic enzyme production by some white-rot fungi. Dye decolorization by selected culture filtrates

Levin L, Melignani E, Ramos AM.

Lab. de Micología Experimental, Dpto. de Biodiversidad y Biología Experimental, Fac. Cs. Exactas y Naturales, PROPLAME – PRHIDEB – CONICET, Universidad de Buenos Aires, C1428EHA Ciudad Universitaria, CABA, Argentina.


The effect of amino acids, complex nitrogen sources and vitamin addition on Trametes trogii, Trametes villosa and Coriolus versicolor var. antarcticus ligninolytic enzyme production, was evaluated. Dye decolorization by their culture filtrates was compared. Glutamic acid followed by peptone, were the best N sources for laccase and manganese peroxidase production. The three fungi produced two laccase isoenzymes (molecular weights from 38 up to 150 kDa); their pattern of production was not affected by medium composition. Although the response was not uniform, vitamin addition sometimes stimulated ligninolytic enzyme production, but never inhibited it. Thiamine induced manganese peroxidase production. T. trogii grown in glutamic acid produced culture filtrates with the highest laccase (188.3 U/ml) and manganese peroxidase activities (4.5 U/ml), rendering the best results in decolorization. These crude filtrates were able to decolorize in half hour (at pH 4.5, 30 degrees C): 13%, 23%, 40%, 46%, 82%, 94% and 95% of Gentian Violet, Xylidine, Congo Red, Malachite Green, Remazol Brilliant Blue R, Indigo Carmine and Anthraquinone Blue, respectively.