Inhibitory effect of IL-8 on insulin action in human adipocytes via MAP kinase pathway.
BACKGROUND
Various cytokines and other compounds are produced in human adipose tissue and might have functions in the adipose tissue. They might be involved in complications associated with obesity and diabetes. Recently, interleukin-8 (IL-8) has been shown to be produced and released from human adipose tissue and/or adipocytes, suggesting IL-8 involvement in some obesity-related health complications. Therefore, we found it of interest to investigate whether IL-8 is involved in the insulin action in human adipocytes.


METHODS
The IL-8 levels in the medium were measured using ELISA. The IL-8 mRNA expression was analyzed using Northern blot analysis. The phosphorylation of Akt was analyzed using Western blot analysis. Furthermore, we examined the effect of IL-8 on the phosphorylation of Akt induced by insulin.


RESULTS
The level of IL-8 in the medium and the IL-8 mRNA expression after stimulation with either TNF-alpha, IL-1beta, or CRP was significantly enhanced in human adipocytes. It is particularly interesting that IL-8 per se also enhanced IL-8 mRNA expression. The IL-8 induced-IL-8 mRNA expression was inhibited by PD98059 (a MEK inhibitor) or SB203580 (a p38 MAPK inhibitor). The IL-8 inhibited insulin-induced Akt phosphorylation. The inhibitory effect of IL-8 was eliminated by either PD 98059 or SB203580.


CONCLUSIONS
These data suggest that IL-8 is a main adipocytokine producing insulin resistance via the inhibition of insulin-induced Akt phosphorylation in adipocytes. The attenuation of IL-8 action might be a target for prevention of diabetes and its complications.
Kobashi
Chikaaki
C
First Department of Internal Medicine, Faculty of Medicine, Toyama University, Toyama, Japan. murakaze@med.u-toyama.ac.jp.
Asamizu
Sachie
S
Ishiki
Manabu
M
Iwata
Minoru
M
Usui
Isao
I
Yamazaki
Katusuya
K
Tobe
Kazuyuki
K
Kobayashi
Masashi
M
Urakaze
Masaharu
M