Phenotypical and functional study of ghrelin and its receptor in the pathogenesis of Crohn's disease.
BACKGROUND
Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor (GHSR), has been demonstrated to possess multiple functions including antiinflammatory effects. The aim of this study was to investigate the expression of ghrelin and GHSR and the function of ghrelin in inflammatory bowel disease (IBD).


METHODS
The expression of ghrelin and GHSR mRNA was quantified in mucosal biopsy specimens from 9 controls, 15 patients with Crohn's disease (CD), and 15 patients with ulcerative colitis (UC) using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The locations of ghrelin and GHSR were investigated immunohistochemically in surgically resected specimens. We also evaluated the percentage of GHSR-positive peripheral blood mononuclear cells (PBMCs) in healthy controls and patients with CD by flow cytometry. In addition, we investigated the immunoregulatory function of ghrelin in peripheral blood T cells.


RESULTS
Ghrelin mRNA levels in colonic mucosa of IBD were higher than control level. The GHSR-1a mRNA level in active CD was also significantly higher than the control level. Ghrelin and GHSR-1a were expressed on CD3- and CD68-positive cells. The percentage of GHSR-1a-positive peripheral blood T cells in patients with CD was significantly higher than the control level. Stimulation of human T cells with ghrelin increased levels of IL-4 and IL-13 proteins and decreased levels of IFN-gamma protein. Reactivity to ghrelin was low in CD compared with the control level.


CONCLUSIONS
Our findings demonstrate that ghrelin may play an important role in the immune system in CD. The dysregulation of reactivity of T cells induced by ghrelin suggests that ghrelin might participate in the pathogenesis of CD.
Hosomi
Shuhei
S
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Oshitani
Nobuhide
N
Kamata
Noriko
N
Sogawa
Mitsue
M
Yamagami
Hirokazu
H
Watanabe
Kenji
K
Tominaga
Kazunari
K
Watanabe
Toshio
T
Fujiwara
Yasuhiro
Y
Maeda
Kiyoshi
K
Hirakawa
Kosei
K
Arakawa
Tetsuo
T
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000235:genetics; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D054439:Ghrelin / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D054439:Ghrelin; D018793:Interleukin-13; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D015847:Interleukin-4; D007371:Interferon-gamma