Intestinal trefoil factor binds to intestinal epithelial cells and induces nitric oxide production: priming and enhancing effects of mucin

The protective effect of Trefoil Factor Family (TFF) proteins in the gastrointestinal tract by promoting the healing of injured mucosa is well known. An increasing body of evidence connects TFFs, especially, TFF2 and TFF3, with a possible role in immune regulation. TFF2 is able to inhibit lipopolysaccharide-induced nitric oxide production in monocytes and can potently limit leukocyte recruitment at the site of injury. An analysis of gene expression in gastrointestinal tissue of TFF2-deficient mice reveals some new aspects of TFF2's role in the immune response.

Section: Tffs and Modulation Of Immune Responsementioning

confidence: 95%

Trefoil factors

Baus-Lončar

Kayademir

Takaishi

et al. 2005

“…This suggested that the decreased colonic contents of nitrated protein and the therapeutic effect of TFF2 in the DNBS model were directly related to a TFF2-mediated decrease in expression of iNOS [81,175]. TFF3, on the other hand, has been reported to increase production of NO via increased expression of iNOS, an effect which is enhanced by mucin [199]. Since NO has multiple functions including cytoprotection and anti-inflammatory effects, these in this respect apparently contrasting properties for TFF2 and TFF3 may not be conflicting [200].…”

Section: Immune Modulationmentioning

confidence: 97%

“…Thus, the combination of TFFs and mucins has been demonstrated to protect cell monolayers against injurious agents, to decrease proton permeation through mucus and to increase mucus viscosity [205 -207]. However, TFF-mucin interactions have also been shown to promote cellular effects like cell migration and NO production [179,199]. Due to variations in their structure, including the shape and numbers of putative mucin binding pockets [37] and free cysteines, it seems likely that each TFF may interact differently with the mucins.…”

Section: Mucin Interactionsmentioning

confidence: 98%

“…for tumor spreading [133]. In accord with a role of the TFFs in restitution, the peptides were all found to enhance migration of intestinal epithelial cell lines [45, 162, Anti-apoptosis 1 -3 IEC18, HCT116, AGS, HT-ITF1, IEC6 [46, 145, 182 -184] Scattering/invasion 1 -3 transformed kidney and colonic cells, Rat-2 non transformed fibroblasts [192,195,196] Migration/restitution 1 -3 IEC6, HT29, monocytes, BEAS-2B, corneal epithelium, oral keratinocytes [45,81,151,162,163,169,179,180,193,194] Angiogenesis 1 -3 Chorioallantoic membrane assay, HUVEC on matrigel [197] Immune modulation 2, 3 Monocytes, IEC18, HT29, T84, IEC6 [81,145,148,199,202] Mucin synergies 2, 3 IEC18, IEC6 [179,199,205] Mucin interactions 1 -3 Yeast two-hybrid, rheometry, proton permeation [173,206,207,209] Enhanced transepithelial resistance 3 HT29/B6 [210] Gastric protection and repair 1 -3 Cryoprobe-, indomethacin-, ethanol-, aspirin-or stress-induced ulcers [45, 163 -168] Intestinal protection and repair 1 -3 DSS-, DNBS-, mitomycin C-, acetic acid-, radiation-or chemotherapy-induced colitis. IL-10 -/-mice, necrotizing enterocolitis model [126, 129, 159, 160, 169 -171, 174, 176, 177] 1358 S. Kjellev Biological and functional properties of TFFs 169,179].…”

Section: Migration and Invasionmentioning

confidence: 99%

See 1 more Smart Citation

The trefoil factor family – small peptides with multiple functionalities

Kjellev¹

2008

234

252

The trefoil factor family (TFF) comprises a group of small peptides which are highly expressed in tissues containing mucus-producing cells - especially in the mucosa lining the gastrointestinal tract. The peptides seem crucial for epithelial restitution and may work via other pathways than the conventional factors involved in restitution. In vitro studies have shown that the TFFs promote restitution using multiple mechanisms. The peptides also have other functionalities including interactions with the immune system. Moreover, therapeutic effects of the TFFs have been shown in several animal models of gastrointestinal damage. Still it is not clear which of their in vitro properties are involved in the in vivo mode of action. This review describes the TFF family with emphasis on their biological properties and involvement in mucosal protection and repair.

“…Fluorescence-activated cell sorting (FACS) analysis of non-enzymatically detached cells incubated at 4 °C indicated that fl uorescein isothiocyanate (FITC)-or phycoerythin-conjugated mouse anti-biotin antibody bound to the outer surface of these cells in a specifi c manner [19], and that the binding was increased by preincubating in mucin (5 mg/ml for 90 min), a situation that resulted in augmented nitric oxide production upon stimulation with rTFF2 (2.5 µM, 18 h). These data were interpreted as showing that the interaction of rTFF3 with IEC-18 cells was upregulated by mucin.…”

Section: Bt-rtff3 Binding To Iec18 Cells Augmented By Mucinmentioning

confidence: 99%

Trefoil factors

Otto

Thim²

2005

Trefoil factor family (TFF) peptides have many in vivo and in vitro effects on restitution, wound healing, apoptosis, cell motility, adhesion and vectorial ion pumping, amongst others. (125)I-TFF peptides bind to cell membranes with classical saturable ability. It would be surprising if there were not TFF-protein interactions that would explain these actions, but to date no convincing TFF-binding partner has been shown which unambiguously takes part in any of these functions. Nevertheless, several TFF-binding proteins exist, including the small intestinal CRP-ductin (muclin), which binds TFF2, and the recently described gastric foveolar proteins TFIZ1 (TFF1-binding) and blottin (TFF2-binding), any of which may yet interact in novel ways to elicit TFF-mediated events. This review describes the expression and, where known, the functions of such proteins.