Vol. 17 No. 1 (2012)English pages

FAX:  +81-3-5472-7526
e-mail:  jsit19@jikei.ac.jp
Deadline for abstract submissions:  June 26, 2012

AN UNKNOWN EPISODEOF THE PIONEER DAYS OFIMMUNOTOXICOLOGY

The theme for this Meeting:  “New aspects of diseases
related to immunotoxicology”

YASUAKI ARAKAWA(National Institute of Occupational Safety and Health, Japan)

First, I would like to thank for the president Junichi
Sawada, board of directors, members of the JapaneseSociety of Immunotoxicology to bestow the title of thehonorary member on me.
At the editorial staff ’s request, here, I would like toreview details and background that I began to have thenotion of immunotoxicology since 1974.
In the field of preventive medicine, at the process ofthe connection and treatment with many environmental
matters, I felt strongly the necessity of forward-looking
countermeasure but not backward countermeasure in the
coming preventive medicine. In addition of that, I began
to feel strongly the necessity of not only general toxic
assessment but also individual toxic assessment of suchbody function as brain-nerve function, immunofunctionand endocrine function.

Program (Tentative Schedule)■September 15, 2012 (Saturday)
・Special Lecture 1:
Prof. Henk van Loveren (Immunotoxicology
Laboratory for Health Protection Research, National
Institute of Public Health and the Environment
・Luncheon Seminar 1:
Dr. Gary Bembridge (Huntingdon Life Sciences Ltd.)・Award Lectures:
Dr. Eiko Koike
Dr. Yasumitsu Nishimura
・Educational Lecture 2:
Prof. Kazuhiro Kondo(Department of Virology, The Jikei University Schoolof Medicine)・Workshop:
In vitro immunotoxicology
Dr. Emanuela Corsini (University of Milan, Italy)
Dr. Hitoshi Sakaguchi (Kao)The 19 Annual Meeting of JSIT 2012(Japanese Society of Immunotoxicology)thDr. Takao Ashikaga (Shiseido)Prof. Setsuya Aiba (Tohoku University School ofMedicine)

September 15–16, 2012

Prof. Ai-Young Lee (Dongguk University, SouthKorea)

Auditorium (Daigaku ichigou-kan), The Jikei University

・Oral / Poster presentation

School of Medicine

・Social gathering

3-25-8 Nishishinbashi, Minato-ku, 105-8461 Tokyo, Japan.

Cafeteria Liebe (TAKAGI Nigo-kan)

Organizing Committee of the 19th Annual Meeting of JSIT
http://jsit19.umin.ne.jp■September 16, 2012 (Sunday)
・Special Lecture 2:

President:

Dr. Motoyasu Ohsawa

Prof. Hiroyuki Yanagisawa, The Jikei University School(Hatano Research Institute, Food and Drug Safetyof Medicine

Center)Secretariat:

・Educational Lecture 2:

Yuichi Miyakoshi and Toshikazu Koiwai, The Jikei

Prof. Toru Miyazaki

University School of Medicine(Laborator y of Molecular Biomedicine forPhone:  +81-3-3433-1111 (ext. 2266)

Pathogenesis, Center for Disease Biology and─ 15 ─

ImmunoTox Letter
led with the inhibition of intracellular phospholipid

Integrative Medicine, Faculty of Medicine, Thetransport between organelles by impairing the structure

University of Tokyo)

and functions of the Golgi apparatus and the ER, and the・Luncheon Seminar 2:

consequent inhibition of phospholipid metabolism andDr. Lawrence D Jacob (Principal Immunologist andinhibition of the membrane-mediated signal transduction

Molecular Biologist, Bioanalysis and Immunology
Group,Charles River Laboratories Preclinicalservices, Edinburgh)system leading to DNA synthesis via phospholipid
turnover and Ca2+ mobilization and finally inhibition ofcell proliferation.

・Symposium:This study on mechanism of dialkyltin-induced thymus

Progress in research for immunotoxicology

atrophy led to the discovery of the suppressive effects

Prof. Kou Sakabe

on malignant cell proliferation system leading to the(Department of Human Structure and Function,

antitumor activity of organotin and the new mechanism

Tokai University School of Medicine)of antitumor system via membrane-mediated signal

Dr. Kenji Ishiwatatransduction.

(Depar tment of T ropical Medicine, The Jikei
University School of Medicine)

Trialkyltin-induced thymus atrophy was caused byapoptosis led with the induction of expression of Fas /Dr. Yasumitsu Nishimura

Fas L, no expression of Bid, decrease in the membrane(Department of Hygiene, Kawasaki Medical School)

potential, followed by high expression of cytochrome c and・Oral presentation / Poster discussion

loss of mitochondrial function (mitochondria involvement),

・Awards Ceremony

and ultimately high increases in the activities of caspase-8,-9, and -3, high expression of CAD (which fragments DNA),no expression of ICAD (CAD inhibitor).

Therefore, I began to aim at construction of scientific

Organotin led to the inhibition of Zn-dependent thymic

learning system of the toxicology to examine andhormone activity and the disorder of differentiation andevaluate individually the toxicity of such biofunction as

maturation of T-lymphocytes in the thymus, followed bybrain-nerve function, immunofunction and endocrine

the disorder of immunoresponse system.
Further, the studies on the phospholipid metabolism-function, and to be necessary for establishment of the risk

mediated signal transduction system advanced toasscessment.
Of all the environmental chemical substances,

the studies on arachidonic acid cascade system, andorganotin compounds were selected as the best

consequently led to the discover y of prostaglandin

substances having the possibility to cause manysystem-mediated anti-inflammatory action of organotin.
In connection with these studies on organotin, manyenvironmental matters in near future and to examine andinternational conferences aiming at the development ofevaluate individually the toxicity of body function.
While inducing the lesion of memory and olfaction, theaging of blood-brain barrier in brain-nerve systems, thea new bioactive substance became to be held in foreigncountries since 1980.

lesion of generative function such as testis atrophy in

In 1984, the International Seminor on theendocrine systems, organotin made a great contribution

Immunological System as a Target for Toxic Damage wasto the study on the toxicology of immunofunction ( We

held at Grand Duchy of Luxenbourg. This was the first

advocated as immunotoxicology since 1974 ) .

conference that immunotoxicology began to be defined

The immunotoxicological study on organotin gave

internationally as one of the domain of research.
In Japan, First Workshop on Heavy Metals Immunotoxicology

many evidences and information by their property takingof Metals (promoted by the Japanese Society for Hygiene ) waspart in every immunoresponse systems.
For example, organotin induced severe thymus atrophyand suppression of T cell dependent immunofunction.

held in 1984. This was the first conference held under the nameof Immunotoxicology in Japan.

Dialkyltin-induced thymus atrophy was due to necrosis
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Our study on “Immunotoxicological Research of

Vol. 17 No. 1 (2012)
Environmental Chemicals” was given in tr ust asenhanced atopic dermatitis-like skin lesions related toGrant Program A (30 million yen) of Grants-in-Aid formite allergen in males, but not in females. In future, I

Scientific Research (KAKENHI) of Monbusho (nowwould like to focus on the effects of maternal exposure

Monbu Kagakusho) (Ministry of Education, Culture,

to environmental chemicals on allergic diseases inSports, Science and Technology) in 1985. This wasdescendants. In addition, I would like to focus on thethe first Government Grant given under the name ofdifference in the susceptibility to chemicals by the sexes.

Immunotoxicology in Japan.
In 1986, I published “Chapter 9: Suppression of cellproliferation by certain organotin compounds” in Tin andReport of the attendance of 51th SOT meeting

Malignant Cell Grouth (CRC Press, Boca, Raton, Florida, USA).

Reiko Teshima

In 1991, I published “Chapter 3: Immunotoxicological(National Institute of Health Sciences)

Test of Metals” in Vol. 10 “Immunotoxicology” of Chairof Toxicological Test (Chijin Shokan). This was the first

The 51th SOT (Society of Toxicology) meeting of USA

publishing in collected form with pharmaceuticals andwas held at Moscone Convention Center in San Francisco

metals as environmental chemicals in Japan.

during March 12-15, 2012.  

After 20 years since 1974 when we advocatedOn the third day (March 14) mor ning, SOT-ISSa s i m m u n o t o x i c o l o g y, t h e J a p a n e s e S o c i e t y o f(Immunotox speciality section) - proposed symposium

Immunotoxicology started in 1994.

“the allergenicity and immunomodulatory effect of foodsubstances” was held.   Dr. Gregory S. Ladics (Dupont
Agricultural Biotechnology, Wilmington, DE, USA) and I
organized the symposium as chairpersons and 5 speakers

Young power for immunotoxicological researchpresented their data and discussed with audiences.

The effects of environmental chemicals ofallergic disorders

and functional biology of allergenic food proteins by

Rie Yanagisawa

Prof. Heimo Breiteneder (Medical Uviversity of Vienna,(National Institute for Environmental Studies)

Vienna,), 2. Role of dietary triglycerides in the immune

When I was a master’s student, I studied murine strain

response to concomitantly ingested protein antigens by

The title of 5 speakers were as follows; 1. Structuraldifferences in allergic airway inflammation following theDr. Eric Eckhardt (University of Kentucky, Lexington,exposure to diesel exhaust particles (DEPs). Since 2000,

KY, USA), 3. Anti-allergic effects of a specific mixture

I have engaged again in the assessment of health effectsof oligosaccharides or combined with a probiotic straincaused by DEPs in National Institute for Environmental(synbiotics) by Dr. Leon Knippels (Danone Research,Studies. DEPs, contain a variety of environmental

Wageningen, Netherlands), 4. Food sensitization and its

chemicals, can enhance various respiratory diseases,

induction by immunomodulating factors by Dr. Tomoko

however, it was not clear which components in DEP are

Shindo (Research Institute, Hadano Kanagawa, Japan),associated with the aggravation of various respiratory

5. In vitro provocation study by Dr. Ryosuke Nakamura

diseases such as allergic airway inflammation. I have

(National Institute of Health Sciences, Japan).

elucidated that extracted organic chemicals in DEP,

The symposium presented several hypotheses

rather than residual carbonaceous nuclei of DEP after

regarding the role that dietar y triglycerides andextraction, exaggerated allergic airway inflammation

synbiotics may play in the development of oral tolerance

through the enhancement of Th2 responses. Next,

as well as the role immunomodulating factors (e.g.,

I undertook the establishment and validation of ‘inenvironmental factors) may play in breaking oral

vivo screening’, which can detect the health effects

tolerance to protein allergens.   Additionally, theof environmental chemicals such as Di-(2-ethylhexyl)

structural and functional biology of allergenic foodphthalate (DEHP). Furthermore, I have elucidated that

proteins were discussed along with in vitro models tomaternal exposure to DEHP during neonatal periods

predict the potential cross-reactivity of food proteins.

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