15-Deoxy-Delta(12,14)-prostaglandin J2 induces IL-8 and GM-CSF in a human airway epithelial cell line (NCI-H292).
BACKGROUND
15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), a major prostanoid metabolized from prostaglandin D2 (PGD2), plays an important role in various biological processes including inflammatory responses. 15d-PGJ2 exerts its effects through two major receptors, chemoattractant receptor- homologous molecule expressed on Th2 cells (CRTH2) and peroxisome proliferator-activated receptor-gamma (PPARgamma). The 15d-PGJ2/PPARgamma system, in particular, regulates numerous biological processes including adipogenesis, apoptosis, and inflammation. Although our studies have shown that PGD2 (metabolic precursor of 15d-PGJ2) induces IL-8 and GM-CSF production, the role of 15d-PGJ2 (metabolite of PGD2) is unknown in human bronchial epithelial cells. In this study, we investigated the function of 15d-PGJ2 on a human airway epithelial cell line: NCI-H292.


METHODS
NCI-H292 cells were cultured in the presence of various stimulants. The resulting supernatants were used for ELISA analysis.


RESULTS
We demonstrated that 15d-PGJ2 induced production of IL-8 and GM-CSF from NCI-H292. 13,14-Dihydro-15-keto-PGD2 (DK-PGD2) (CRTH2 agonist) and troglitazone (PPARgamma agonist) failed to increase the production of these cytokines. Pretreatment with ramatroban (CRTH2 antagonist) and GW9662 (PPARgamma antagonist) did not reduce the production of these cytokines. 15d-PGJ2 activated the ERK1/2 signaling pathway in a time-dependent manner.


CONCLUSIONS
These data showed that 15d-PGJ2 is a potent inducer of IL-8 and GM-CSF production through ERK1/2 kinase activation, but this is independent of CRTH2 or PPARgamma activation.
Chiba
Takahito
T
Department of Dermatology, Kyushu University School of Medicine, Fukuoka, Japan.
Ueki
Shigeharu
S
Ito
Wataru
W
Kato
Hikari
H
Takeda
Masahide
M
Kayaba
Hiroyuki
H
Furue
Masutaka
M
Chihara
Junichi
J
D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D016209:Interleukin-8; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D015230:Prostaglandin D2