The increased expression of an array of C-X-C and C-C chemokines in the colonic mucosa of patients with ulcerative colitis: regulation by corticosteroids.
OBJECTIVE
To better understand the extent to which chemokines participate in the mucosal inflammatory response in patients with ulcerative colitis (UC), we assessed the expression of an array of chemokines in the colonic mucosa of UC patients and evaluated the effect of corticosteroids on their expression.


METHODS
Colonic mucosal biopsy specimens were obtained from 15 patients with UC and 12 normal controls. Messenger RNA levels for 10 chemokines were quantitated by reverse transcription polymerase chain reaction using synthetic standard RNAs. The biopsy specimens were also cultured in the presence or absence of tumor necrosis factor alpha (TNFalpha) and/or dexamethasone, and secreted chemokines in culture supernatants were assayed by ELISA.


RESULTS
The messenger RNA expression of C-X-C (interleukin 8, growth-related alpha [GROalpha], GRObeta, GROgamma, epithelial cell-derived neutrophil activator 78, and interferon-gamma-inducible protein 10) and C-C (monocyte chemotactic protein 1, macrophage inflammatory protein 1beta, and RANTES [regulated on activation, normal T-cell expressed and secreted]) but not C (lymphotactin) chemokines was significantly higher in the affected mucosa of UC patients than in the unaffected mucosa of UC patients or in the normal mucosa of normal controls. The degree of increased expression was more prominent in the C-X-C than in the C-C chemokines. Further, the secretion of interleukin 8, GROalpha, epithelial cell-derived neutrophil activator 78, and monocyte chemotactic protein 1 was higher in UC patients than in normal controls, induced significantly by TNFalpha, and down-regulated by dexamethasone. Secretions of macrophage inflammatory protein 1beta and RANTES also showed a trend toward an increase in UC, induction by TNFalpha, and down-regulation by dexamethasone, but it did not reach statistical significance.


CONCLUSIONS
The increased expression of a variety of chemokines in UC and their downregulation by dexamethasone suggest that chemokines may play an important role in the immunopathogenesis of UC.
Yang
Suk-Kyun
SK
Department of Internal Medicine and Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Choi
Myung-Sik
MS
Kim
Ok-Hee
OH
Myung
Seung Jae
SJ
Jung
Hwoon-Yong
HY
Hong
Weon-Seon
WS
Kim
Jin Ho
JH
Min
Young Il
YI
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001707:Biopsy, Needle; D019742:Chemokines, CC / Q000032:analysis / Q000378:metabolism*; D019743:Chemokines, CXC / Q000032:analysis / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000473:pathology*; D003113:Colonoscopy; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis*; D012016:Reference Values; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019742:Chemokines, CC; D019743:Chemokines, CXC; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone