ImmunoTox Letter
ImmunoTox Letter DigestDecember,
2014

Report from the 21st Annual Meeting of theJapanese Society of Immunotoxicology(JSIT2014)
Seiichiro Himeno
Tokushima Bunri University, Fac. of Pharmaceutical Sci.

The 21st Annual Meeting of the Japanese Society of

The 22nd Annual Meeting of JSIT 2015
(Japanese Society of Immunotoxicology)
September 10–11, 2015
Kyoto University,
Clock Tower Centennial Hall International Conference Hall,
Kyoto-city, Japan.
Access:Immunotoxicology (JSIT2014) was held at International

http://www.kyoto-u.ac.jp/ja/access/campus/map6r_y.htm

Conference Hall, Tokushima Bunri University, Tokushima,

Yoshida-Honmachi, Sakyo-ku, Kyoto, 606-8501

during September 11-12, 2014. The main theme of thismeeting was “A Step forward in Imunnotoxicological

Theme:Studies”. The meeting consists of 2 special lectures, 1“Revolutionary perspectives in the field of immunotoxicity

educational lecture, symposium, workshop, 2 luncheon-Toxic effects and Distrupting effects-”

seminars, JSIT Research Award Lecture, 15 oralpresentations and 23 poster presentations including 5

The details of the 22nd Annual Meeting of JSIT 2015

student and young scientist presentations.

are now under preparation. Two special lectures, 1
symposium, 1 educational lecture, and 1 workshop will
be held.

Special lecture
1. Immunotoxicity of biologics. (Marc Pallardy, UniversiteParis-Sud, France)

Deadline for abstract submission:

2. The mechanisms for zinc deficiency-associated dermatitis.

June 26, 2015 (a tentative plan)(Tatsuyoshi Kawamura, University of Yamanashi,
Department of Dermatology, Kofu, Japan)

President:
Environmental Health Division,

Educational lecture

Department of Environmental Engineering,

1. Molecular pathogenesis of hyper-IgE syndrome.

Graduate School of Engineering,(Yoshiyuki Minegishi, Institute for Genome Research,

Kyoto UniversityThe University of Tokushima, Tokushima, Japan)

Kyoto daigaku-Katsura, Nishikyo-ku, Kyoto 615-8540
Prof. Hirohisa Takano

Symposium“Next-generation Approach in Immunotoxicology”

Secretariat:

1. Dynamics of complex biological systems determined/

Akiko Honda

controlled by minimal subsets of molecules in regulatory

Phone: +81-75-383-3342

networks. (Atsushi Mochizuki, Theoretical Biology

Fax: +81-75-383-3344

Laboratory, RIKEN, Japan)

Email: jsit22-office@health.env.kyoto-u.ac.jp

2. Chemical strategy for direct and indirect detectionof protein-small molecule interactions: Drug target

Website: http://health.env.kyoto-u.ac.jp/jsit22-office(under construction)

discovery and P450 substrate screening. (Naoki Kanoh,Graduate School of Pharmaceutical Sciences, TohokuUniversity, Japan)
3. A novel role of spleen-derived IL-10 in obesity-induced
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Vol. 19 No. 2 (2014)
Photos: http://p.bunri-u.ac.jp/jsit2014/photo.html

systemic inflammation. (Koro Gotoh, Faculty ofMedicine, Oita University, Japan)
4. New mechanism of action and potential biomarkers
for vaccine adjuvant. (Ken J Ishii, Laboratory ofAdjuvant Innovation, National Institute of Biomedical

The Best Presentation AwardInnovation, Japan)

Effects of intratracheal exposure
to bisphenol A on the immune systemand central nervous system in a murine
model of allergic airway inflammation

Workshop on Immunotoxicology Methods“Toward the development of new test methods forxenobiotic-induced allergy and autoimmune diseases”
1. Autoimmune disorders and side-effects via immune

Eiko Koike1, Rie Yanagisawa1,
Tin Tin Win Shwe1, Hirohisa Takano2

systems that are caused by administering biotechnologyderived pharmaceuticals. (Tomoaki Inoue, Chugai

National Institute for Environmental Studies, 2Kyoto University

1Pharmaceutical Co. Ltd., Japan)
2. Splenic lesion in rats treated with antithyroid drugs –Recently, experimental and epidemiological studies

suggestive auto-antibody production. (Motoko Fukui,raise concerns about endocrine disruption and allergy

ASKA Pharmaceutical Co., Japan)

related to exposure to chemicals in consumer products.

3. Animal model of immediate hypersensitivity induced

Bisphenol A (BPA) is an environmental chemical whichby transdermal administration of food allergen. (Reikoexhibits hormone-like properties. BPA is widely used in

Adachi, National Institute of Health Science, Japan)

the manufacture of polycarbonate plastics and epoxy

4. The study of detection method for particulate

resins. These materials are found in some consumer

environmental chemical-induced respiratory allergy.

products and food containers. BPA is being increasingly(Risako Nishino, The Institute of Environmental

associated with adverse health effects including allergy

Toxicology, Japan)such as asthma in children.
In the present study, we investigated the effects ofIn this year, “JSIT Research Award” was received

intratracheal exposure to BPA (0.0625, 1.25, 25 nmol/by Dr. Motoyasu Ohsawa (Hatano Research Institute,body/wk) on the immune system and central nervous

Food and Drug Safety Center). Title: Immunotoxicity ofsystem using an allergic airway inflammation model

environmental substances with special reference to heavy

induced by ovalbumin (OVA) in 6-week-old C3H/HeJ Jcl

metals: Toxicological properties and evaluation. “Themale mice. Following exposure to BPA, the changes ofBest Presentation Award” was received by Dr. Eiko Koike

several parameters of the immune system and central(National Institute for Environmental Studies). Title:

nervous system were examined.

Effects of intratracheal exposure to bisphenol A on theCo-exposure to OVA and BPA (low- and medium-immune system and central nervous system in a murinedose) significantly enhanced airway inflammation andmodel of allergic airway inflammation. “The Student

Th2 cytokine production such as IL-13, IL-33, KC, andand Young Scientists Award” was given to Mr. Toshihiro

RANTES, compared with OVA alone. OVA-specific Ig (IgE,Hirai (Graduate School of Pharmaceutical Sciences, Osaka

IgG1, IgG2a) production was also tended to enhance byUniversity), Title: The effects of metal nanoparticles onco-exposure to OVA and BPA. In lung local lymph nodes,

onset of metal allergy, and Dr. Seiji Onuma (Graduate

total cell numbers and Th2 cytokine production (IL-4

School of Pharmaceutical Sciences, Chiba University),and IL-5) were significantly greater in the OVA+BPA

Title: Preventive effects of the histamine H 4 receptor(low- and medium-dose) group than in the OVA group.

antatonist on worsening of itching induced by long-term

Central nervous system parameters were examined only

topical glucocorticoid treatment.

in the high-dose BPA. OVA+BPA group had poorer ability

I would like to appreciate all the participants who
actively joined presentations and discussions.

to discriminate between old and new objects by novelobject-recognition test than the vehicle or BPA group.

No.2（15） 29

ImmunoTox Letter
Preventive effect of the histamine H4
receptor antagonist on worseningof itching induced by long-term topicalglucocorticoid treatment

Moreover, memory function-related gene expression(NMDA receptor subunit NR2B) in hippocampus was also
decreased in the OVA+BPA group compared with thevehicle group. These results suggest that BPA exposure

Seiji Onuma

throughout childhood may disrupt immune responses andcentral nervous system function in allergic mice.

Department of Geriatric Pharmacology and Therapeutics,
Graduate School of Pharmaceutical Sciences, Chiba University

I’m very honored to receive the Students & Young
Scientist Award at the 21st Annual Meeting of JSIT 2014. I

The Student and Young
Scientists Award

would like to sincerely thank you to the committee.
Topical application of glucocorticoid (GC) is the firstline therapy for the treatment of chronic skin diseases.

The effects of metal nanoparticles
on onset of metal allergy

However, long-term topical GC often increases side

Toshiro Hirai

effects, even pruritus (itching). Previously, we reported

Laboratory of Toxicology and Safety Science,that long-term topical GC application to TNCB-induced

Graduate School of Pharmaceutical Sciences,chronic dermatitis model mice exacerbated pruritus1).

Osaka University, Osaka, Japan

Histamine is one of the mediators of pruritus andhistamine H 4 receptor (H 4R) is gathering attention

I am very privileged to receive the students/young
scientist best presentation award at the 21stannual

meeting of the Japanese Society of Immunotoxicology andas “pruritus receptor.” In this study, we investigatedwhether H 4R antagonist could suppress pruritus of
glucocorticoid-induced pruritus model mice.

would like to appreciate the support from the selection

Oral administration of JNJ39758979 or JNJ28307474,committee. I would also like to give special thanks tothe selective H4R antagonists, decreased scratching

my research professor Dr. Yasuo TSUTSUMI, Dr. Yasuo

counts, the index of pruritus, of TNCB-induced chronicYOSHIOKA, Dr. Kazuma HIGASHISAKA and otherdermatitis model mice. Furthermore, JNJ28307474

colleagues in Laboratory of Toxicology and Safety Sciencesignificantly decreased ear thickness of mice, the index

for supporting throughout the progress.

of inflammation, which was significantly suppressed by

Until now, metal ions have been thought to be an onlyrepeated DEX application. From these results, it wasform of metal which penetrate into our body. However,indicated that H4R antagonists could be useful drug forthe recent study revealed that not only ions, but also

preventing exacerbation of pruritus induced by long-term

metal nanoparticles, which could penetrate our barrier,topical glucocorticoid treatment.

were naturally occurred from bulk metal. In this study,

I would also like to express my greatest gratitude

we investigate the effects of metal nanoparticles on onset

to Prof. Akihiro HISAKA, Assoc. Prof. Katsunoriof metal allergy compared with the effect of metal ions.

YAMAURA, Res. Assoc. Hiromi SATO and emeritus Prof.

In the results, we showed that the metal nanoparticles

Koichi UENO. Additionally, I would like to give special

were stronger sensitizer than metal ions and could be thethanks to Janssen Research & Development, LLC forcause of onset of metal allergy. We hope that our results

generous provision of H4R antagonists.

contribute the future prevention of metal allergy.
Reference1) Yamaura et al. J Toxicol Sci. 2011; 36(4): 395-401

No.2（16） 30

Vol. 19 No. 2 (2014)
discovery and P450 substrate screening” from Dr. Naoki

Symposium Report

Kanoh (Graduate School of Pharmaceutical Sciences,Tohoku University, Japan), about chemical biology fromCompletion of the symposium titled
Next-generation Approachin Immunotoxicology

basic to advanced study. Their unique technology thatenables small molecules to be conjugated to a solid phaseby a functional group-independent manner convinced

Eiko Koike , Ryosuke Nakamura ,Yasumitsu Nishimura3, Yasuo Yoshioka4
1

2

Center for Environmental Health Sciences,1

us that the chemical biology has a great potential not
only to explore target molecules but also to evaluate
immunotoxicity of drug candidates.

National Institute for Environmental Studies, Japan

Next, Dr. Koro Gotoh (Faculty of Medicine, Oita

Division of Medicinal Safety Science,University) gave us a lecture on “A novel role of spleen-2

National Institute of Health Sciences, Japanderived IL-10 in obesity-induced systemic inflammation”

Department of Hygiene, Kawasaki Medical School,including a preventive point of view. In his talk, inability

Kurashiki, Japanof the spleen to synthesize anti-inflammatory IL-10

Laboratory of Toxicology and Safety Science,

was shown to induce systemic chronic inflammation inGraduate School of Pharmaceutical Sciences,obesity. Because the contribution of the environmental

Osaka University, Osaka, Japanpollutants is concerned for the increase of lifestyle-At the 21 st annual meeting of JSIT, Tokushima,development of the new immunotoxicological study for

we’ve organized and completed the symposium titledthe elucidation of the toxicological mechanism is needed.

“Next Generation’s Study for Immunotoxicology”. At

At last, Dr. Ken J Ishii (National Institute of Biomedical

the beginning of plan about this symposium, we had

Innovation) gave us a lecture on “New mechanism of34

related chronic inflammatory diseases, we learned

reconfirmed the increases in hazardous risks derived

action and potential biomarkers for vaccine adjuvant”.

from current progress of sciences and techniques and

The actual mechanisms of vaccine adjuvants have been

the newly accumulated information about relationshipnot immunologically understood for a long time, with

between immune functions and diseases, resulting in thea famous sarcastic remark “Immunologist’s dirty little

conclusion that we had to learn borderless sciences andsecret”, although the research and development ofreinforce Immunotoxicology more. Therefore, the present

adjuvants has a history of more than 80 years. In his talk

symposium was focused and organized on the points ofabout the novel mechanisms of several adjuvants, we“prevention”, “exploration”, “resolution” and “application”,

learned the strong relationship between the research ofin which we could have listened the four interesting andvaccine adjuvant and immunotoxicity.

highly suggestive talks.
First, Dr. Atsushi Mochizuki (Theoretical Biology
Laboratory, RIKEN, Japan) gave us his special talk, titled“Dynamics of complex biological systems determined/

Young power for immunotoxicological researchcontrolled by minimal subsets of molecules in regulatorynetworks”. In his talk, the networks of biological molecules

Effects of inflammatory cytokines on
accumulation of manganesein human neuronal cells

and genes and the relationships among them wereexplained in a simple manner by mathematical methods,
which allowed us to recognize the significance of those

Hitomi Fujishiro

theoretical techniques to obtain clear-cut conclusion fromLaboratory of Molecular Nutrition and Toxicology,

various kinds of OMICS analyses.

Faculty of Pharmaceutical Sciences, Tokushima Bunri University

Next, we had an intelligible presentation titled“Chemical strategy for direct and indirect detection

Exposure to an excess amount of manganese (Mn) causesof protein-small molecule interactions: Drug target

neurological symptoms similar to Parkinson’s disease.

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ImmunoTox Letter
Zinc (Zn) transporters such as Zrt, Irt-related protein 8

induced immunotoxicology under the mentorship of(ZIP8), and ZIP14 have been shown to have affinities forProfessor Seiichiro Himeno.

Mn as well as Zn, but their roles in Mn uptake in neuronal

Arsenic is an environmental pollutant derived fromcells remain unclear. The introduction of siRNA of ZIP14

the Earth’s crust. Populations around the world havedecreased the uptake of Mn, suggesting an important role

been exposed to arsenic-polluted well water and therebyof ZIP14 in Mn uptake in human SH-SY5Y neuroblastoma

chronic arsenic poisoning, which causes hyperkeratosis,cells. The pretreatment of SH-SY5Y cells withcancer, diabetes, cardiovascular disease, and otherinterleukin-6 (IL-6) markedly increased the accumulationdiseases. I have been examining the hypothesis thatof Mn, which could be partly explained by the increased

chronic exposure to arsenic gives rise to these disorders

uptake of Mn

due to IL-6-induced up-regulation ofvia dysfunctions of the immune system. My results

ZIP8 and ZIP14. The treatment of SH-SH5Y cells withindicate that the functions of natural killer (NK) cells

IL-6 clearly decreased the expression level of ZnT10 andand T cells are affected by arsenic exposure. I am

decreased the Mn excretion efficiency. Pretreatment ofcurrently investigating the mechanisms underlying theSH-SH5Y cells with TNFα or IL-1β also up-regulated

dysfunctions of NK cells, T cells, and immunologicalgene expression of ZIP8 and ZIP14, and decreased thefunction among individuals chronically exposed to arsenicmRNA levels of ZnT10. Thus, the enhancement of thein Bangladesh.

2+

production of inflammatory cytokines in the brain

I will do my best to make meaningful contributions

might be related the aberrant Mn accumulation and theto the Japanese Society of Immunotoxicology. I hope todevelopment of neurodegenerative disorders.

inspire your further guidance and encouragement.

Mineral oil exposure and humanautoimmunity

Words from new councilors

Minoru Satoh, MD, PhD

Greetings to becoming
a new councilor member

Professor

Daigo Sumi

Department of Clinical Nursing

Faculty of Pharmaceutical Sciences, Tokushima Bunri University

School of Health Sciences
University of Occupational and Environmental Health, JapanAt the beginning, I would like to take this opportunity
to express my gratitude to the doctors and seniors who

I would like to thank members of the Board ofrecommended and accepted me as a councilor member ofDirectors of the JSIT for accepting me to serve as athe Japanese Society of Immunotoxicology.

councilor. I started my career as a rheumatologist for 10

I obtained a Ph.D. with a research focus on the anti-years before moving to the United States for research inatherosclerotic effects of nitric oxide at the Graduate

1991. My original plan was to spend 2-3 years there andSchool of Medicine of Nagoya University. After graduation,

come back to continue my career as a rheumatologist-

I worked for 3 years as a Post Doctoral Fellow at theresearcher, however, I ended up spending 22 years for

Dr. Louis J. Ignarro (a 1998 Nobel Laureate in Medicine)research in the US until I took a position at University

Laboratory at the David Geffen School of Medicine atof Occupational and Environmental Health (UOEH) lastUCLA. Following that work, I undertook the study ofyear. Throughout my career, I have been working on

biological reactions involving environmental chemicals

clinical significance and mechanisms of autoantibody

at Tsukuba University (Professor Yoshito Kumagai

production, in particular role of chemicals and otherLaboratory). More recently, I joined the Faculty ofenvironmental factors in autoimmunity. A mouse model

Pharmaceutical Sciences at Tokushima Bunri University,of lupus-like autoimmunity we discovered, induced by awhere I have been investigating various aspects of metal-component of mineral oil pristane, became a standard

No.2（18） 32

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model of chemically-induced lupus. Since the roles ofmineral oil exposure in induction of autoimmunity inhuman have not been well studied, I would like to focus
my future research on this area, taking an advantageof the unique environment of UOEH and with help
from members of the JSIT. I will continue to work on
autoimmunity using an international network andcontribute to the research in immunotoxicology andthe JSIT from a view of a rheumatologist specialized inautoantibody research.

As the councilor of the Japanese Societyof Immunotoxicology
Takamasa Kido
Department of Public Health and Environmental Medicine,
The Jikei University School of Medicine

I take very honored to be the councilor of the JapaneseSociety of Immunotoxicology. I would like to thankProfessor Yanagisawa, Dr. Tsunoda and seniors who
recommended my appointment to the committee of theJapanese Society of Immunotoxicology.
During my graduate student days in the master course
at Kitasato University Graduate School of MedicalSciences, I focused on the immunotoxicity of petroleumderived cleaning solvent for dry cleaning in in vitro
study. The mRNA expressions of cytokines related toinflammation and allergy in J774.1 cells exposed to thecleaning solvent or PCE were elevated.
In addition, I participated in the study evaluating thetoxicity of multi-walled carbon nanotubes (MWCNT). My
role in the study was the evaluation of mRNA expressionsin splenocytes after whole body inhalation of MWCNT.
Relative mRNA expression of IL-1β in macrophages
from the female rats exposed to 5 mg MWCNT/m3
was significantly higher than in control rat cells. For
lymphocytes, the cells from male and female rats in theMWCNT-exposed groups had significantly lower IL-2
values than control rat cells.
I continues the study for immunotoxicity of essentialtrace element, zinc as Research assistant at Departmentof Public Health and Environmental Medicine, The Jikei
University, School of Medicine.
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