Prostaglandin D2 induces IL-8 and GM-CSF by bronchial epithelial cells in a CRTH2-independent pathway.
BACKGROUND
Prostaglandin D(2) (PGD(2)), a major prostanoid produced by activated mast cells, has long been implicated in allergic diseases. PGD(2) demonstrates its effects through two G-protein-coupled receptors, DP and CRTH2. The PGD(2)/CRTH2 system mediates chemotaxis of eosinophils, basophils, and Th2 cells, which are involved in the induction of allergic inflammation. Although recent studies have shown that the specific receptors for PGD(2), DP, and CRTH2 are expressed in various human tissues, the role of PGD(2) is unknown in human bronchial epithelial cells. In this study, we investigated the expression and function of CRTH2/DP on NCI-H(292) and NHBE cells.


METHODS
The CRTH2/DP expression was examined by RT-PCR and flow-cytometric analysis. NCI-H(292) and NHBE cells were cultured in the presence of various stimulants. The resulting supernatants were measured by ELISA.


RESULTS
We demonstrated that PGD(2) induced production of IL-8 and GM-CSF in NCI-H(292) and NHBE cells. DK-PGD(2) (CRTH2 agonist) and latanoprost (FP, a prostaglandin F receptor, agonist) failed to augment the production of these cytokines. Pretreatment with ramatroban (CRTH2 antagonist) and AL8810 (FP antagonist) did not reduce the production of these cytokines. The PGD(2)-induced cytokine production was inhibited by pertussis toxin or specific inhibitors for MAP/ERK kinase (PD98059) and p38 MAP kinase (SB202190).


CONCLUSIONS
These results suggest that PGD(2) is a potent inducer of IL-8 and GM-CSF production with MAP/ERK and p38 MAP kinase activation, but this is independent of CRTH2 activation.
Chiba
Takahito
T
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
Kanda
Akira
A
Ueki
Shigeharu
S
Ito
Wataru
W
Kamada
Yumiko
Y
Oyamada
Hajime
H
Saito
Norihiro
N
Kayaba
Hiroyuki
H
Chihara
Junichi
J
D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D015230:Prostaglandin D2 / Q000494:pharmacology / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D016209:Interleukin-8; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor