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Interleukin‐18 prevents apoptosis via PI3K/Akt pathway in normal human keratinocytes
Author(s) -
HOSOTANI Yuka,
KASHIWAMURA ShinIchiro,
KIMURASHIMMYO Akiko,
SEKIYAMA Atsuo,
UEDA Haruyasu,
IKEDA Tomohiro,
MIMURA Osamu,
OKAMURA Haruki
Publication year - 2008
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.2008.00513.x
Subject(s) - xiap , protein kinase b , ly294002 , pi3k/akt/mtor pathway , apoptosis , cancer research , phosphorylation , chemistry , cytokine , microbiology and biotechnology , biology , signal transduction , caspase , immunology , biochemistry , programmed cell death
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 α‐chain neutralizing antibody increased apoptosis and caspase‐3 activity. Exogenous IL‐18 augmented phosphorylation of Akt and activation of NF‐κB. The promotion of Akt phosphorylation by IL‐18 was abolished by LY294002, a PI3K inhibitor, but not SN50, an NF‐κB inhibitor, indicating that IL‐18 functions via the PI3K/Akt pathway and independently of NF‐κB. 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 α‐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.