Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants|
Environmental physiology (including Physical medicine and Nutritional physiology)
|Research Institution||KYUSHU UNIVERSITY|
HORI Tetsuro Kyushu University, Dept.of Physiology, Professor, 大学院・医学系研究科, 教授 (00022814)
TAKAKI Atsushi Kyushu University, Dept.of Physiology, Assistant Professor, 大学院・医学系研究科, 助手 (30243934)
KATAFUCHI Toshihiko Kyushu University, Dept.of Physiology, Assistant Professor, 大学院・医学系研究科, 講師 (80177401)
AOU Shuji Kyushu University, Dept.of Physiology, Assistant Professor, 大学院・医学系研究科, 助教授 (40150908)
TAKE Sachiko Kyushu University, Dept.of Physiology, Assistant Professor, 大学院・医学系研究科, 助手 (80253425)
|Project Period (FY)
1998 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥31,600,000 (Direct Cost : ¥31,600,000)
Fiscal Year 1999 : ¥4,800,000 (Direct Cost : ¥4,800,000)
Fiscal Year 1998 : ¥26,800,000 (Direct Cost : ¥26,800,000)
|Keywords||brain-gut-liver-immune interaction / endotoxin / c-fos / antisense-oligo DNA / CRF / cytokines / flowcytometer / immobilization stress / 脳・免疫系連関 / 脳・腸・肝・免疫系軸 / Bacterial Translocation / インターロイキン-1β / インターロイキン6 / 脳内ノルアドレナリン / 痛覚系 / プロスタグランディンE2|
In this project, we intended to claryfy the central and peripheral mechanisms in terms of host defense functions under non-inflammatory environmental stress. Main results are summarized as follows.
1) Proposal of a new host-defense paradigm/the brain-gut-liver-immune axis
The non-inflammatory stress induced the change of gut membrane barrier sysytem, then gut-derived endotoxin come into the inside of the barrier sysytem (stress-induced LPS translocation). Stress-induced LPS translocation in the gut acitivate the immune network resulting in up regulation of the host=defense function againt the stress.
2) The effect of brain-derived IL-1 on the noradrenargic (NA) sysytem
The release of NA in the frontal brain during the immobilization stress is mediated by the IL-I, PGE2, NO, and Glutamate.
3) Modification of brain-derived cytokines on the mechanisms of notiception
Administration of cytokines into the brain changed the threshold the notiception.
4) Expression of cytokines and c-fos in the brain during the non-inflammatory stresses
The c-fos mRNA expression in the POA, LHA, VMH in the brain was increased by cold exposure. The CRF mRNA expression in the MPO and PVN was increased by heat exposure, and that in the POA and LHA was increased by cold exposure. The microinjection of the antisense-oligo DNA for the c-fos into the POA inhibited the expression of IFN mRNA in the brain.
5) The shift of subsets of periferal lymphocytes during the non-inflammatory stresses
The head down stress during one hour induced the CD4+ Tcell increase, CD4/8 increase. However, six hour later, CD8+ T cell decrease and B cell increase was observed.