transforming-growth-factor-beta and Cat-Diseases

Feline autologous mesenchymal stem cells (MSCs) show promise for immunomodulatory activity, but the functional impact of chronic kidney disease (CKD), concurrent immunosuppressive drug administration or infection is unknown. The study objectives compare endogenous cytokine gene expression (interleukin [IL]-6, IL-10, IL-12p40, IL-18 and transforming growth factor beta [TGF-β]) in adipose-derived MSCs (aMSCs) from cats with and without CKD, following in vitro exposure to microbial ligands and treatment with common immunosuppressive drugs.. Previously obtained aMSCs, phenotype CD44. aMSCs isolated from healthy and CKD cats showed no significant differences in gene expression in the five measured cytokines. No significant changes in measured gene expression after drug treatment or microbial ligand stimulation were observed between normal or CKD affected cats. Proinflammatory genes (IL-6, IL-12p40 and IL-18) showed altered expression in aMSCs from both groups when compared with the same cells in standard culture after exposure to methotrexate. Poly I:C altered IL-6 and TGF-β gene expression in aMSCs from both healthy and CKD cats when compared with the same cells in standard culture.. The five genes tested showed no statistical differences between aMSCs from healthy or CKD cats. There was altered cytokine gene expression between the control and treatment groups of both healthy and CKD cats suggesting feline aMSCs have altered function with immunosuppressive treatment or microbial ligand exposure. Although the current clinical relevance of this pilot study comparing brief exposure to select agents in vitro in aMSCs from a small number of cats is unknown, the study highlights a need for continued investigation into the effects of disease and concurrent therapies on use of cell-based therapies in feline patients.

Topics: Adipose Tissue; Animals; Cat Diseases; Cats; Cytokines; Gene Expression; Interleukin-12 Subunit p40; Interleukin-18; Interleukin-6; Ligands; Mesenchymal Stem Cells; Methotrexate; Pharmaceutical Preparations; Pilot Projects; Poly I; Renal Insufficiency, Chronic; Transforming Growth Factor beta

The aim of this study was to evaluate the role of angiotensin II (AT-II) and its main mediator, transforming growth factor beta 1 (TGF-β1), in the development of feline renal fibrosis.. Expression of marker genes indicating epithelial-to-mesenchymal transition (EMT), profibrotic mediators and matricellular proteins was measured in feline kidney epithelial cells (Crandell Rees feline kidney [CRFK] cells) after incubation with AT-II and/or TGF-β1.. Cells incubated with TGF-β1 or the combination of TGF-β1 with AT-II showed clear EMT with more stretched fibroblastic cells, whereas the cells incubated without TGF-β1 and AT-II (control) showed more epithelial cells. Gene expression of collagen type I (. TGF-β1 significantly induced expression of the EMT marker gene α-SMA, profibrotic mediator

Topics: Angiotensin II; Animals; Cat Diseases; Cats; Cell Line; Epithelial Cells; Epithelial-Mesenchymal Transition; Kidney; Kidney Diseases; Transforming Growth Factor beta

CD8(+) lymphocytes are critical to the control and elimination of viral pathogens. Impaired CD8(+) responses are well recognized in lentiviral infections; however, the mechanisms underlying CD8(+) impairment remain elusive. Using the feline immunodeficiency virus (FIV) model for human AIDS, we reported previously that CD4(+)CD25(+) Treg cells in both the acute and long-term, asymptomatic phase of infection are constitutively activated and suppress CD4(+)CD25(-) T cell responses. In the current study, we have demonstrated that CD4(+)CD25(+) Treg cells suppress CD8(+) responses to immune stimulation during both the acute and chronic, asymptomatic phase of FIV infection and that the mechanism of suppression may be mediated by membrane-associated TGF-beta (mTGF-beta) on CD4(+)CD25(+) lymphocytes. Depletion of CD4(+)CD25(+) lymphocytes from lymph node suspensions significantly enhanced production of IFN-gamma during the acute phase of infection and coculture of CD8(+) lymphocytes with CD4(+)CD25(+) lymphocytes resulted in suppression of CD8(+) IFN-gamma during both the acute and chronic stages of infection. FACS analysis indicated that there was TGF-betaRII upregulation on CD8(+) cells from FIV(+) cats during the acute and chronic stage of infection. In addition, there was upregulation of mTGF-beta on the CD4(+)CD25(+) subset in chronically infected cats. In support of activation of the TGF-beta signaling pathway, Western blotting showed Smad 2 phosphorylation in CD8(+) targets following CD4(+)CD25(+)/CD8(+) coculture. These results demonstrate the suppressive effect CD4(+)CD25(+) Treg cells have on the CD8(+) immune response during the acute and chronic stages of FIV infection and suggest that the mechanism of suppression may be mediated by mTGF-beta.

Topics: Animals; Cat Diseases; Cats; CD4 Antigens; CD8-Positive T-Lymphocytes; Immune Tolerance; Immunodeficiency Virus, Feline; Interferon-gamma; Interleukin-2 Receptor alpha Subunit; Lentivirus Infections; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

Transforming growth factor-beta1 (TGF-beta1), an inflammatory cytokine, plays a role in tissue fibrosis, such as glomerular sclerosis and tubulointerstitial fibrosis of the kidneys. In the present study, the urinary TGF-beta1 level of cats diagnosed with chronic renal failure (CRF) was measured to investigate its relationship to the pathogenesis of feline CRF. Urinary TGF-beta1 levels (TGF-beta1/creatinine ratio) were significantly increased compared with healthy controls, whereas serum levels of TGF-beta1 were not. These results indicate that TGF-beta1 is expressed in the kidneys of CRF cats, and that it was reflected in the urinary TGF-beta1 level. Therefore, TGF-beta1 may play a role in feline CRF, and urinary TGF-beta1 could be used as a clinical marker for renal fibrosis.

Topics: Animals; Biomarkers; Cat Diseases; Cats; Creatine; Kidney; Kidney Failure, Chronic; Transforming Growth Factor beta; Transforming Growth Factor beta1