PMID- 18789072
OWN - NLM
STAT- MEDLINE
DCOM- 20081104
LR  - 20211203
IS  - 0385-2407 (Print)
IS  - 0385-2407 (Linking)
VI  - 35
IP  - 8
DP  - 2008 Aug
TI  - Interleukin-18 prevents apoptosis via PI3K/Akt pathway in normal human 
      keratinocytes.
PG  - 514-24
LID - 10.1111/j.1346-8138.2008.00513.x [doi]
AB  - Interleukin-18 (IL-18) is a pleiotropic cytokine expressed in both immune and 
      non-immune cells. In the present study, we demonstrate an anti-apoptotic role of 
      IL-18 in normal human neonatal foreskin epidermal keratinocytes (NHEK-F). 
      Cultured NHEK-F spontaneously produced the active form of IL-18. Treatment of 
      NHEK-F cells with anti-IL-18 receptor alpha-chain neutralizing antibody increased 
      apoptosis and caspase-3 activity. Exogenous IL-18 augmented phosphorylation of 
      Akt and activation of NF-kappaB. The promotion of Akt phosphorylation by IL-18 
      was abolished by LY294002, a PI3K inhibitor, but not SN50, an NF-kappaB 
      inhibitor, indicating that IL-18 functions via the PI3K/Akt pathway and 
      independently of NF-kappaB. In addition, IL-18 was found to augment expression of 
      anti-apoptotic proteins, Bcl-2, XIAP and glucose regulated protein78/BiP, while 
      anti-IL-18 receptor alpha-chain neutralizing antibody suppressed expression of 
      Bcl-2, XIAP, glucose regulated protein94 and protein disulfide isomerase. Taken 
      together, these results indicate that IL-18 plays an important role in 
      keratinocyte survival.
FAU - Hosotani, Yuka
AU  - Hosotani Y
AD  - Department of Ophthalmology, Institute for Advanced Medical Sciences, Hyogo 
      College of Medicine, Nishinomiya, Hyogo, Japan.
FAU - Kashiwamura, Shin-Ichiro
AU  - Kashiwamura S
FAU - Kimura-Shimmyo, Akiko
AU  - Kimura-Shimmyo A
FAU - Sekiyama, Atsuo
AU  - Sekiyama A
FAU - Ueda, Haruyasu
AU  - Ueda H
FAU - Ikeda, Tomohiro
AU  - Ikeda T
FAU - Mimura, Osamu
AU  - Mimura O
FAU - Okamura, Haruki
AU  - Okamura H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Dermatol
JT  - The Journal of dermatology
JID - 7600545
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (Molecular Chaperones)
RN  - 0 (NF-kappa B)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XIAP protein, human)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Caspase 3/metabolism
MH  - Cells, Cultured
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - *Epidermal Cells
MH  - Heat-Shock Proteins/metabolism
MH  - Humans
MH  - Infant, Newborn
MH  - Interleukin-18/*pharmacology/physiology
MH  - Keratinocytes/*physiology
MH  - Molecular Chaperones/metabolism
MH  - NF-kappa B/metabolism
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphorylation/drug effects
MH  - X-Linked Inhibitor of Apoptosis Protein/metabolism
EDAT- 2008/09/16 09:00
MHDA- 2008/11/05 09:00
CRDT- 2008/09/16 09:00
PHST- 2008/09/16 09:00 [pubmed]
PHST- 2008/11/05 09:00 [medline]
PHST- 2008/09/16 09:00 [entrez]
AID - JDE513 [pii]
AID - 10.1111/j.1346-8138.2008.00513.x [doi]
PST - ppublish
SO  - J Dermatol. 2008 Aug;35(8):514-24. doi: 10.1111/j.1346-8138.2008.00513.x.