The proinflammatory CXC-chemokines GRO-α/CXCL1 and MIG/CXCL9 are concomitantly expressed in ulcerative colitis and decrease during treatment with topical corticosteroids
- Arne EgestenAffiliated withDepartment of Clinical Sciences Lund Email author
- , Mette EliassonAffiliated withDepartment of Clinical Sciences Lund
- , Anders I. OlinAffiliated withDepartment of Clinical Sciences Lund
- , Jonas S. ErjefältAffiliated withDepartment of Clinical Sciences Lund
- , Anders BjartellAffiliated withDepartment of Clinical Sciences Malmö, Lund University, University Hospital MalmöDepartment of Urology, Memorial Sloan-Kettering Cancer Center
- , Per SangfeltAffiliated withDepartment of Medical Sciences, Gastroenterology Research Group, Uppsala University
- , Marie CarlsonAffiliated withDepartment of Medical Sciences, Gastroenterology Research Group, Uppsala University
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Ulcerative colitis is characterized by relapsing mucosal inflammation where the lesions include tissue-damaging granulocytes. In addition, T cells and natural killer (NK) cells play important pathophysiologic roles. Chemokines are a large family of peptides that play key roles in the regulation of inflammation. The CXC-chemokines, growth-related oncogene (GRO)-α/CXCL1 and interleukin (IL)-8/CXCL8, both recruit neutrophils and possess mitogenic properties, whereas the interferon-dependent CXC-chemokines monokine induced by gamma-interferon (MIG)/CXCL9, interferon-γ inducible protein of 10 kD/CXCL10, and IFN-inducible T cell alpha chemoattractant/CXCL11 recruit and activate T cells and NK cells.
Materials and methods
The expression of CXC-chemokines was studied in eight controls and in 11 patients suffering from ulcerative colitis in the distal part of the colon, before and during topical treatment with corticosteroids. Perfusates (obtained before, after 7 days, and after 28 days of treatment) and pinch biopsies (obtained before and after 28 days of treatment) were collected by colonoscopy. The rectal release of GRO-α and MIG was determined by enzyme-linked immunosorbent assay (ELISA), and tissue expression of the chemokines was detected in colonic tissue by immunohistochemistry.
In perfusates, high levels of GRO-α, IL-8, and MIG were detected compared with controls (p = 0.02, 0.005, and p = 0.03, respectively). During treatment with corticosteroids, both GRO-α and MIG decreased. In clinical nonresponders, characterized by sustained inflammation, the levels of GRO-α and MIG remained elevated. Both epithelial cells and granulocytes, present in the submucosa, expressed GRO-α and MIG as detected by immunohistochemistry.
CXC-chemokines are likely to be important in the pathophysiology of ulcerative colitis and may become targets for novel treatment strategies. In addition, GRO-α may serve as a marker of disease activity.
KeywordsUlcerative colitis GRO-α/CXCL1 MIG/CXCL9 Chemokines Corticosteroids
- The proinflammatory CXC-chemokines GRO-α/CXCL1 and MIG/CXCL9 are concomitantly expressed in ulcerative colitis and decrease during treatment with topical corticosteroids
International Journal of Colorectal Disease
Volume 22, Issue 12 , pp 1421-1427
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- Ulcerative colitis
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- 1. Department of Clinical Sciences Lund, BMC B14, Tornavagen 10, 221 84, Lund, Sweden
- 2. Department of Clinical Sciences Malmö, Lund University, University Hospital Malmö, Malmö, Sweden
- 4. Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
- 3. Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden