Soluble galectin-3 is a strong, colonic epithelial-cell derived, lamina propria fibroblast-stimulating factor

Elisabeth Lippert ^1*, Werner Falk ¹, Frauke Bataille ², Thilo Kähne ³, Michael Naumann ³, Michael Goeke ⁴, Hans Herfarth ¹, Juergen Schoelmerich ¹ and Gerhard Rogler ¹

¹ Department of Internal Medicine I, University of Regensburg, Germany
² Insitute of Pathology, University of Regensburg, Germany
³ Institute of Experimental Internal Medicine, Otto-von-Guericke University, Magdeburg, Germany
⁴ Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule, Hannover, Germany

^* To whom correspondence should be addressed. E-mail: elisabeth.lippert{at}web.de.

Accepted 10 May 2006

Abstract

Background & Aims: Colonic lamina propria fibroblasts (CLPFs) play an important role in the pathogenesis of fibrosis and strictures in Crohn's disease (CD). Our goal was to identify colonic epithelial cells (CEC)-derived factors that activate CLPFs.

Methods: Primary human CECs and CLPFs were isolated from control mucosa and IL-8 of CLPF cultures was quantified by ELISA. Activation of NF-B was demonstrated, and translocation of NF-B was inhibited by a dominant negative IB-expressing adenovirus. The major CLPF-activating (IL-8 inducing) protein was purified using FPLC (HiPrep 16/60 Sephacryl S- 200 High Resolution Column) and SDS gel electrophoresis.

Results: A significant increase of IL-8 secretion by CLPFs cultured in CEC-conditioned media compared to unconditioned media (155,000 ± 10,000pg/ml versus 1,434 ± 695 pg/ml) was found. The effect of CEC-conditioned media on CLPF IL-8 secretion was NF-B dependent. A protein/DNA array confirmed involvement of NF-B as well as AP-1. Purification of a candidate band isolated using SDS-PAGE and subsequent sequencing revealed soluble galectin-3 to be this strong CLPF- activating factor. Depletion of galectin-3 from conditioned media by IP abolished the CLPF stimulatory effect.

Conclusions: Using a classical biochemical approach, we identified soluble galectin-3 as a strong activator of CLPFs produced by CEC. Galectin-3 induced NF- B activation and IL-8 secretion in these cells and may be a target for future therapeutic approaches to reduce or avoid fibroblast activation.

Keywords: cytokines, epithelial cells, fibroblasts, galectin-3, IBD

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