Streptococcal Preparation (OK-432) Inhibits Development of Type I Diabetes in NOD Mice

Toyota, Takayoshi; Satoh, Jo; Oya, Koki; Shintani, Shigeki; Okano, Tsuyoshi

doi:10.2337/diab.35.4.496

Cited by 75 publications

(41 citation statements)

References 5 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NK cells of NOD mice have been described as functionally deficient. This characteristic is attributed as a result of observations that NOD NK cells lyse the prototype NK target cell, Yac-1, less efficiently than NK cells of other mouse strains (61,62). Determining the extent of the NOD NK deficiency will require a comprehensive analysis of NK lytic potential and cytokine production in response to additional target cell types.…”

Section: Discussionmentioning

confidence: 99%

Ly-49P Activates NK-Mediated Lysis by Recognizing H-2Dd 1

Silver

Gong

Chang

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Little is known regarding the ligand specificity of Ly-49 activating receptor subfamily members expressed by NK cells. A new Ly-49 activating receptor related to Ly-49A in its extracellular domain, designated Ly-49P, was recently cloned from 129 strain mice. We independently cloned an apparent allele of Ly-49P expressed by nonobese diabetic and nonobese diabetes-resistant mouse strain NK cells. We found it to be reactive with the A1 Ab thought to recognize a polymorphic epitope expressed only by the Ly-49A inhibitory receptor of the C57BL/6 strain. Rat RNK-16 cells transfected with Ly-49P mediated reverse Ab-dependent cellular cytotoxicity of FcR-positive target cells, indicating that Ly-49P can activate NK-mediated lysis. We determined that RNK-16 lysis of Con A blasts induced by Ly-49P was MHC dependent, resulting in efficient lysis of H-2Dd-bearing targets. We found that the Dd α1/α2 domain is required for Ly-49P-mediated RNK-16 activation, as determined by exon shuffling and transfection. Thus, Ly-49P is the second activating Ly-49 receptor demonstrated to induce NK cytotoxicity by recognizing a class I MHC molecule.

show abstract

Section: Discussionmentioning

confidence: 99%

Ly-49P Activates NK-Mediated Lysis by Recognizing H-2Dd 1

Silver

Gong

Chang

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Complete Freund's adjuvant [84] Streptococcal OK-432 [85] Klebsiella pneumonia glycoprotein [86] Escherischia coli LPS [86] Zymosan [87] Zymosan [88] CpG DNA [89] CpG DNA [90] Polyinosinic:polycytidylic acid [80] OM-85 (multi-species extract) [91] Pseudomonas aeruginosa OdDHL [92] Legend: LNFPIII -lacto-N-fucopentaose III, BCG -baccilus calmette-guerin, LPS -lipopolysaccharide, OdDHL -N-(3-oxododecanoyl)-L-homoserine lactone.…”

Section: Bovis Bcg [82 83]mentioning

confidence: 99%

Helminth Infection and Type 1 Diabetes

Zaccone¹,

Hall²

2012

Rev Diabet Stud

View full text Add to dashboard Cite

■ AbstractThe increasing incidence of type 1 diabetes (T1D) and autoimmune diseases in industrialized countries cannot be exclusively explained by genetic factors. Human epidemiological studies and animal experimental data provide accumulating evidence for the role of environmental factors, such as infections, in the regulation of allergy and autoimmune diseases. The hygiene hypothesis has formally provided a rationale for these observations, suggesting that our coevolution with pathogens has contributed to the shaping of the present-day human immune system. Therefore, improved sanitation, together with infection control, has removed immunoregulatory mechanisms on which our immune system may depend. Helminths are multicellular organisms that have developed a wide range of strategies to manipulate the host immune system to survive and complete their reproductive cycles successfully. Immunity to helminths involves profound changes in both the innate and adaptive immune compartments, which can have a protective effect in inflammation and autoimmunity. Recently, helminth-derived antigens and molecules have been tested in vitro and in vivo to explore possible applications in the treatment of inflammatory and autoimmune diseases, including T1D. This exciting approach presents numerous challenges that will need to be addressed before it can reach safe clinical application. This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation.

show abstract

“…Therefore, the beta-cell damage is theoretically preventable through inhibition of the serial reactions, as indicated by shaded arrows. One method is by inhibiting abnormal immune reactions with immunomodulators such as cyclosporin, linomide and OK-432 [68,69]. Others are scavenging the radicals, which break DNA, by superoxide dismutase and other radical scavengers and inhibiting the poly (ADP-ribose) synthetase by specific inhibitors such as nicotinamide and 3-aminobenzamide to prevent the decrease in the NAD + level [36]).…”

Section: +mentioning

confidence: 99%

The CD38-cyclic ADP-ribose signalling system in insulin secretion: molecular basis and clinical implications

1997

View full text Add to dashboard Cite

In answer to the comments of Islam and Berggren concerning our hypothesis on the CD38-cyclic ADPribose (cADPR) signalling system, we will present several lines of evidence that we believe can explain the discrepancies between their view and ours. The Okamoto model and cADPRGlucose is the primary stimulus of insulin secretion and synthesis in pancreatic beta cells of the islets of Langerhans [1±3]. Increases in the intracellular Ca 2+ concentration mediate the biochemical events that couple glucose stimulation to insulin secretion, and mobilization of Ca 2+ from intracellular stores in the endoplasmic reticulum as well as Ca 2+ influx from extracellular sources are important in this process [4]. Concerning the mechanism of Ca 2+ influx from extracellular sources, it has been proposed that ATP generated in the process of glucose metabolism inhibits the ATP-sensitive K + channel, causing beta cell membrane depolarization, thereby opening the voltagedependent Ca 2+ channel and resulting in Ca 2+-influx from the extracellular space [5]. However, it was thought that inositol 1, 4, 5-trisphosphate (IP 3 ) is a second messenger for Ca 2+ mobilization from intracellular stores [6]. Since 1981, we have proposed a model for beta cell damage and its prevention as shown in Figure 1; that is, diabetogenic agents such as streptozotocin and alloxan damage DNA, activating poly(ADP-ribose) synthetase which uses NAD + as a substrate [2, 7±12]. Consequently, intracellular levels of NAD + fall dramatically, causing the inhibition of cellular functions such as insulin synthesis and secretion, and the beta cell ultimately dies. Although insulin-dependent diabetes mellitus (IDDM) can be caused by many different agents such as immunologic abnormalities, inflammatory tissue damage and betacytotoxic chemical substances, the final pathway for the toxic agents is the same, as shown in Figure 1. Therefore, IDDM is theoretically preventable by suppressing immune reactions, scavenging free radicals, and inhibiting the poly (ADP-ribose) synthetase by nicotinamide and 3-aminobenzamide. The question then arises as to why maintaining the cellular NAD + level is essential for beta cells to secrete and synthesize insulin. Since 1987, a metabolite of NAD + , cADPR, has been reported to be as potent and powerful a releaser of intracellular Ca 2+ as IP 3 in a variety of cells [13±29]. In 1993, we found that the cADPR level increased in pancreatic islets in response to glucose stimulation and that cADPR released Ca 2+ from the microsomes, suggesting that cADPR has a second messenger role in insulin secretion [15]. Furthermore, we found that the cADPR level was not increased by glucose stimulation in pancreatic islets pretreated with streptozotocin [15]. When poly(ADP-ribose) synthetase inhibitors such as nicotinamide and 3-aminobenzamide were present, the cADPR level increased with glucose stimulation even in the presence of streptozotocin. These results suggest that cADPR is synthesized from NAD + by glucose stimulation in beta cells [12,15]. We have t...

show abstract

Streptococcal Preparation (OK-432) Inhibits Development of Type I Diabetes in NOD Mice

Cited by 75 publications

References 5 publications

Ly-49P Activates NK-Mediated Lysis by Recognizing H-2Dd 1

Ly-49P Activates NK-Mediated Lysis by Recognizing H-2Dd 1

Helminth Infection and Type 1 Diabetes

The CD38-cyclic ADP-ribose signalling system in insulin secretion: molecular basis and clinical implications

Contact Info

Product

Resources

About