Butyrate blocks interferon-gamma-inducible protein-10 release in human intestinal subepithelial myofibroblasts.
BACKGROUND
Interferon (IFN)-gamma-inducible protein (IP)-10 is a chemoattractant for CXCR 3-expressing T lymphocytes and monocytes. IP-10 has been reported to mediate chronic inflammation such as that in inflammatory bowel disease (IBD). However, the local secretion of IP-10 in the intestine remains unclear. In this study, we investigated IP-10 secretion in human colonic subepithelial myofibroblasts (SEMFs).


METHODS
IP-10 secretion was determined by enzyme-linked immunosorbent assay (ELISA), and IP-10 mRNA expression was evaluated by Northern blotting.


RESULTS
Interleukin (IL)-10 mRNA was not detected in unstimulated SEMFs. Interferon (IFN)-gamma strongly induced IP-10 mRNA expression. Tumor necrosis factor (TNF)-alpha also stimulated IP-10 mRNA expression, but this was much weaker than that induced by IFN-gamma. The effects of IFN-gamma and TNF-alpha were detected in a dose- and time-dependent manner. These responses were also observed at the protein levels. The IFN-gamma-induced IP-10 secretion was not affected by acetate or propionate, but was significantly reduced by butyrate. Trichostatin A, a specific inhibitor of histone deacetylase, also blocked the IFN-gamma- and TNF-alpha-induced IP-10 mRNA expression, but the effects of trichostatin A were weaker than those of butyrate. The inhibitory effect of butyrate on IFN-gamma-induced IP-10 release was not associated with STAT (signaling transducer and activator of transcription)-1alpha activation.


CONCLUSIONS
We demonstrated that human colonic SEMFs are the local site for the secretion IP-10. The regulation of IP-10 release by IFN-gamma and butyrate may play an important role in controlling chronic mucosal inflammation in pathological entities such as IBD.
Inatomi
Osamu
O
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, 520-2192, Japan.
Andoh
Akira
A
Kitamura
Ken-Ichi
K
Yasui
Hirofumi
H
Zhang
Zhuobin
Z
Fujiyama
Yoshihide
Y
D001483:Base Sequence; D015152:Blotting, Northern; D002087:Butyrates / Q000494:pharmacology*; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D008969:Molecular Sequence Data; D032390:Myoblasts, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002087:Butyrates; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma