The effect of interferon gamma on conventional fractionated radiation-induced damage and fibrosis in the pelvic tissue of rabbits

Abstract

We aim to investigate the effect of interferon gamma (IFN-γ) on conventional fractionated radiation–induced damage and fibrosis in ureter and colorectal mucosa. Fifty-two rabbits were randomly divided into three groups comprising a conventional radiation group, an IFN-γ group, and a control group. X-rays were used to irradiate the pelvic tissues of the rabbits in the IFN-γ and conventional radiation groups. Five days after radiation exposure, the rabbits in the IFN-γ group were administered 250,000 U/kg IFN-γ intramuscularly once a week for 5 weeks. The rabbits in the conventional radiation group received 5.0 mL/kg saline. The rabbits were sacrificed at 4, 8, 12, and 16 weeks postradiation, and the rectal and ureteral tissues within the radiation areas were collected. The results showed that the morphology of rectal and ureteral tissues was changed by X-ray radiation. The degree of damage at 4, 8, and 12 weeks, but not at 16 weeks, postradiation was significantly different between the IFN-γ and conventional radiation groups. The expression of transforming growth factor beta 1 mRNA in the ureter and colorectal mucosa of the IFN-γ group was significantly lower than that in the conventional radiation group at 4, 8, 12, and 16 weeks postradiation, but it was still higher than that in the control group. There were significant differences in the expression of collagen III among the three groups. IFN-γ can inhibit the radiation-induced upregulation of transforming growth factor beta 1 mRNA and collagen III protein in the ureter and colorectal mucosa and attenuate radiation-induced damage and fibrosis.

Platelet-Rich Plasma and Bone Marrow-Derived Mesenchymal Stromal Cells Prevent TGF-β1-Induced Myofibroblast Generation but Are Not Synergistic when Combined: Morphological in vitro Analysis

“…However, an involvement of VEGF-A can be postulated taking into consideration that VEGF-A is released by bone marrowderived MSCs [Sassoli et al, 2012] and that the role of VEGF-A in inhibiting myofibroblast differentiation, independently, or at least in part independently, from its ability to negatively regulate TGF-β1 signaling, has been demonstrated [Chellini et al, 2018]. On the other hand, other paracrine factors of MSC secretome may negatively interfere with TGF-β1 signaling, synergistically acting as anti-fibrotic agents such as basic fibroblast growth factor, interleukin-15 and interferon-gamma [Sassoli et al, 2012;Yang et al, 2016;Gallego-Muñoz et al, 2017;Manohar et al, 2018]. Moreover, we have recently demonstrated the expression and release of functional MMP-2 by bone marrow MSCs and their autocrine regulation by the sphingosine 1-phosphate (S1P)/S1P receptor axis [Sassoli et al, 2014a[Sassoli et al, , 2018a.…”

Cytokine Interferon‐γ suppresses the function of capsule myofibroblasts and induces cell apoptosis

“…Extensive studies on the effect of IFN‐γ on MFs have been performed in culture and in animal models demonstrating that IFN‐γ may reduce collagen formation during liver and renal fibrosis . In an animal model it was shown that IFN‐γ inhibited the radiation‐induced upregulation of TGF‐β1 mRNA and collagen III protein in the ureter and colorectal mucosa and attenuated radiation‐induced damage and fibrosis . In a rat model of postlaminectomy peridural fibrosis Emmez et al could provide evidence that topical application of low‐dose IFN‐γ is an effective method of preventing peridural fibrosis .…”

“…Extensive studies on the effect of IFN‐γ on MFs have been performed in culture and in animal models demonstrating that IFN‐γ may reduce collagen formation during liver and renal fibrosis . In an animal model it was shown that IFN‐γ inhibited the radiation‐induced upregulation of transforming growth factor beta (TGF‐β) 1 mRNA and collagen III protein in the ureter and colorectal mucosa and attenuated radiation‐induced damage and fibrosis . In human fibroblastic cell lines Tanaka et al could prove that IFN‐γ blocked the generation of MFs and moderately inhibited the production of α‐SMA in TGFβ1‐promoted MFs indicating that IFN‐γ may be effective in the early stage of contractile diseases to prevent the progression of contractile lesions.…”