Inflammation Location, But Not Type, Determines the Increase in TGF-β1 and IGF-1 Expression and Collagen Deposition in IBD Intestine

Lawrance, Ian C.; Maxwell, Lesley; Doe, William F.

doi:10.1097/00054725-200102000-00003

Cited by 120 publications

(102 citation statements)

References 35 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6 TGF-b1 is also involved in modulation of intestinal inflammation. 7 Dendritic cells (DCs) are antigen-presenting cells with the unique ability to induce primary immune responses. 8 Mature DCs are potent antigen-presenting cells, but immature DCs (imDCs) have been shown to have no or lower expression of costimulatory molecules and exhibit tolerogenicity.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells

Cai

Zhang²,

Li³

et al. 2010

Cell Mol Immunol

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is caused by an uncontrolled immune response in the intestinal lumen, leading to inflammation in genetically predisposed individuals. Immunotherapy may be a promising approach to the treatment of IBD. Here, we show that transforming growth factor-b1 (TGF-b1) gene-modified immature dendritic cells (imDCs) could enhance the inhibitory function of imDCs and delay the progress of IBD induced by dextran sodium sulfate in mice. The results of fluorescence-activated cell sorter (FACS) demonstrated that this protective effect is mediated partially by inducing CD4 1 Foxp3 1 regulatory T cells (Tregs) in mesentery lymph nodes to control inflammation. In vitro experiments also supported this hypothesis. In conclusion, we provide evidence that TGF-b1-modified bone marrow-derived imDCs may have a therapeutic effect to IBD.

show abstract

Section: Introductionmentioning

confidence: 99%

TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells

Cai

Zhang²,

Li³

et al. 2010

Cell Mol Immunol

View full text Add to dashboard Cite

show abstract

“…Although this cytokine acts on promoting immunosuppression and impeding the development of autoimmune conditions, TGF-b, together with IL-6, promotes the differentiation of pathogenic Th17 cells. 39,40 Otherwise, concerning this and other classical antiinflammatory or Th2 cytokines such as IL-10 and IL-4, a significant increase in IL-10 was detected only in groups that received CY alone, suggesting that its production together with TGF-b, in the absence of inflammatory signals, probably lead to regulatory actions, thus inhibiting the incoming inflammatory responses in colitis mice treated only with CY. Surprisingly, TGF-b was increased in all groups, both diseased and treated, at all the time periods, except for 60 days after chemotherapy and BMC infusion.…”

Section: Discussionmentioning

confidence: 98%

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Godoi

Cardoso

Ferraz

et al. 2010

Bone Marrow Transplant

View full text Add to dashboard Cite

Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4 þ leukocytes in the inflammatory infiltrate on days þ 7 and þ 14 and of CD8 þ cells on day þ 7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that highdose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.

show abstract

“…Upregulation of IGF-I expression is a common feature of chronically inflamed intestine whether in animal models of colitis or in Crohn's disease (16,24,37). Within the muscle layer, IGF-I plays an important role in the regulation of smooth muscle cell growth: it jointly stimulates growth and inhibits apoptosis (10,11).…”

Section: Discussionmentioning

confidence: 99%

Endogenous IGF-I and α_vβ₃ integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis

Hazelgrove

Flynn²,

Qiao³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Hazelgrove KB, Flynn RS, Qiao LY, Grider JR, Kuemmerle JF. Endogenous IGF-I and ␣v␤3 integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol 296: G1230 -G1237, 2009. First published April 9, 2009 doi:10.1152/ajpgi.90508.2008.-Endogenous insulinlike growth factor-I (IGF-I) regulates intestinal smooth muscle growth by concomitantly stimulating proliferation and inhibiting apoptosis. IGF-I-stimulated growth is augmented by the ␣v␤3 integrin ligands vitronectin and fibronectin. IGF-I expression in smooth muscle is increased in both TNBS-induced colitis and Crohn's disease. We hypothesized that intestinal inflammation increased vitronectin and fibronectin expression by smooth muscle and, along with IGF-I upregulation, increased intestinal muscle growth. Intestinal smooth muscle cells were examined 7 days following the induction of TNBS-induced colitis. Although ␣ v␤3 integrin expression was not altered by TNBSinduced colitis, vitronectin and fibronectin levels were increased by 80 Ϯ 10% and 90 Ϯ 15%, above control levels, respectively. Basal IGF-I receptor phosphorylation in inflamed muscle from TNBStreated rats was increased by 86 Ϯ 8% over vehicle-treated controls. Basal ERK1/2, p70S6 kinase, and GSK-3␤ phosphorylation in muscle cells of TNBS-treated rats were also increased by 140 -180%. TNBS treatment increased basal muscle cell proliferation by 130 Ϯ 15% and decreased apoptosis by 20 Ϯ 2% compared with that in vehicletreated controls. The changes in proliferation and apoptosis were reversed by an IGF-I receptor tyrosine kinase inhibitor or an ␣v␤3 integrin antagonist. The results suggest that smooth muscle hyperplasia in TNBS-induced colitis partly results from the upregulation of endogenous IGF-I and ligands of ␣ v␤3 integrin that mediate increased smooth muscle cell proliferation and decreased apoptosis. This paper has identified one mechanism regulating smooth muscle hyperplasia, a feature of stricture formation that occurs in the chronically inflamed intestine of TNBS-induced colitis and potentially Crohn's disease.

show abstract

Inflammation Location, But Not Type, Determines the Increase in TGF-β1 and IGF-1 Expression and Collagen Deposition in IBD Intestine

Abstract: These findings suggest that TGF-beta1 and IGF-1 are involved in intestinal ECM remodeling in IBD, and their enhanced expression depends on the presence and location of inflammatory infiltrates rather than the type of IBD.

Cited by 120 publications

References 35 publications

TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells

TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Endogenous IGF-I and α_vβ₃ integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis

Contact Info

Product

Resources

About

Inflammation Location, But Not Type, Determines the Increase in TGF-β1 and IGF-1 Expression and Collagen Deposition in IBD Intestine

Abstract: These findings suggest that TGF-beta1 and IGF-1 are involved in intestinal ECM remodeling in IBD, and their enhanced expression depends on the presence and location of inflammatory infiltrates rather than the type of IBD.

Cited by 120 publications

References 35 publications

TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells

TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Endogenous IGF-I and αvβ3 integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis

Contact Info

Product

Resources

About

Endogenous IGF-I and α_vβ₃ integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis