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The proinflammatory CXC-chemokines GRO-α/CXCL1 and MIG/CXCL9 are concomitantly expressed in ulcerative colitis and decrease during treatment with topical corticosteroids

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Abstract

Background

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.

Results

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.

Conclusions

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.

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Acknowledgments

We are grateful for statistical advice from Mikael Åström, technical assistance of Pia Andersson, and linguistic revision by Dr. Alan Chester. The study was supported by grants from The Bergh, Grönberg, Ihre, Julin, Kock, and Österlund foundations.

Competing interests

None declared.

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Authors and Affiliations

  1. Department of Clinical Sciences Lund, BMC B14, Tornavagen 10, 221 84, Lund, Sweden

    Arne Egesten, Mette Eliasson, Anders I. Olin & Jonas S. Erjefält

  2. Department of Clinical Sciences Malmö, Lund University, University Hospital Malmö, Malmö, Sweden

    Anders Bjartell

  3. Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden

    Per Sangfelt & Marie Carlson

  4. Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Anders Bjartell

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  1. Arne Egesten
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  2. Mette Eliasson
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  3. Anders I. Olin
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  4. Jonas S. Erjefält
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  5. Anders Bjartell
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  7. Marie Carlson
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Correspondence to Arne Egesten.

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Egesten, A., Eliasson, M., Olin, A.I. et al. The proinflammatory CXC-chemokines GRO-α/CXCL1 and MIG/CXCL9 are concomitantly expressed in ulcerative colitis and decrease during treatment with topical corticosteroids. Int J Colorectal Dis 22, 1421–1427 (2007). https://doi.org/10.1007/s00384-007-0370-3

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  • DOI: https://doi.org/10.1007/s00384-007-0370-3

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