Analysis of cytokine functions in graft rejection by gene expression profiles1

Liang, Yurong; Christopher, Kenneth B.; DeFina, Rachel; Cidado, Justin; He, Hongzhen; Haley, Kathleen J.; Perkins, David L.

doi:10.1097/01.tp.0000093464.72920.7c

Cited by 7 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The initial development of antigen-specific cells into Th1 or Th2 phenotype and their stimulation by proinflammatory cytokines including IL-18 may be critical for the subsequent differentiation of inflammatory cells recruited specifically at the site of alloresponse [21]. Our data demonstrated upregulation of IL-18 production in patients with acute rejection of kidney allograft as compared to subjects with uncomplicated outcome or less advanced injury of kidney parenchyma manifested as acute tubulointerstitial nephropathy.…”

Section: Discussionmentioning

confidence: 50%

Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft

et al. 2005

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 50%

Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft

et al. 2005

View full text Add to dashboard Cite

“…A recent study using a functional genomics approach with A␤-stimulated murine microglial cells identified cathepsin B as a key protein mediating microglial neurotoxicity [17]. In the present study, we report on gene expression changes in human microglia isolated from postmortem brain tissues, which were stimulated with aggregated/oligomeric A␤ and subjected to gene expression profiling using microarray hybridization analysis on oligonucleotide DNA arrays with content covering essentially all expressed human genes.…”

Section: Introductionmentioning

confidence: 94%

Gene expression changes by amyloid β peptide-stimulated human postmortem brain microglia identify activation of multiple inflammatory processes

Walker

Link

Lue

et al. 2005

Journal of Leukocyte Biology

157

134

View full text Add to dashboard Cite

A central feature of the inflammatory pathology in Alzheimer's disease is activated microglia clustered around aggregated amyloid beta (Abeta) peptide-containing plaques. In vitro-cultured microglia can be activated to an inflammatory state by aggregated Abeta with the induction of a range of different neurotoxic factors and provide a model system for studying microglia Abeta interactions. Gene expression responses of human postmortem brain-derived microglia to aggregated Abeta were measured using whole genome microarrays to address the hypothesis that Abeta interactions with human microglia primarily induce proinflammatory genes and not activation of genes involved in Abeta phagocytosis and removal. The results demonstrated that Abeta activation of microglia induced a large alteration in gene transcription including activation of many proinflammatory cytokines and chemokines, most notably, interleukin (IL)-1beta, IL-8, and matrix metalloproteinases (MMP), including MMP1, MMP3, MMP9, MMP10, and MMP12. All of these genes could amplify ongoing inflammation, resulting in further neuronal loss. Changes in expression of receptors associated with Abeta phagocytosis did not match the changes in proinflammatory gene expression. Time-course gene expression profiling, along with real-time polymerase chain reaction validation of expression changes, demonstrated an acute phase of gene induction for many proinflammatory genes but also chronic activation for many other potentially toxic products. These chronically activated genes included indoleamine 2,3-dioxygenase and kynureninase, which are involved in formation of the neurotoxin quinolinic acid, and S100A8, a potential proinflammatory chemokine. These studies show that activation of microglia by Abeta induces multiple genes that could be involved in inflammatory responses contributing to neurodegenerative processes.

show abstract

“…However, T1 implantation did not cause a significant increase in anti-Gal IgM and IgA levels in GGTA1 KO mice [17]. Therefore, G/i DKO mice may present a more sensitive model than the GGTA1 KO mice [34]. Our study showed IL-6 and IFN-γ expressions in the T1 group were significantly higher than those in T2 and control, indicating that IL-6 and IFN-γ could serve as sensitive indicators of immunogenicity of xenogeneic bone matrix.…”

Section: Discussionmentioning

confidence: 91%

GGTA1/iGb3S Double Knockout Mice: Immunological Properties and Immunogenicity Response to Xenogeneic Bone Matrix

Shao

Ling

Liang

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Background. Animal tissues and tissue-derived biomaterials are widely used in the field of xenotransplantation and regenerative medicine. A potential immunogenic risk that affects the safety and effectiveness of xenografts is the presence of remnant α-Gal antigen (synthesized by GGTA1 or/and iGb3S). GGTA1 knockout mice have been developed as a suitable model for the analysis of anti-Gal antibody-mediated immunogenicity. However, we are yet to establish whether GGTA1/iGb3S double knockout (G/i DKO) mice are sensitive to Gal antigen-positive xenoimplants. Methods. α-Gal antigen expression in the main organs of G/i DKO mice or bovine bone substitutes was detected via a standardized ELISA inhibition assay. Serum anti-α-Gal antibody titers of G/i DKO mice after immunization with rabbit red blood cells (RRBC) and implantation of raw lyophilized bone substitutes (Gal antigen content was 8.14±3.17×1012/mg) or Guanhao Biotech bone substitutes (50% decrease in Gal antigen relative to the raw material) were assessed. The evaluation of total serum antibody, inflammatory cytokine, and splenic lymphocyte subtype populations and the histological analysis of implants and thymus were performed to systematically assess the immune response caused by bovine bone substitutes and bone substitute grafts in G/i DKO mice. Results. α-Gal epitope expression was reduced by 100% in the main organs of G/i DKO mice, compared with their wild-type counterparts. Following immunization with RRBC, serum anti-Gal antibody titers of G/i DKO mice increased from 80- to 180-fold. After subcutaneous implantation of raw lyophilized bone substitutes and Guanhao Biotech bone substitutes into G/i DKO mice, specific anti-α-Gal IgG, anti-α-Gal IgM, and related inflammatory factors (IFN-γ and IL-6) were significantly increased in the raw lyophilized bone substitute group but showed limited changes in the Guanhao Biotech bone substitute group, compared with the control. Conclusion. G/i DKO mice are sensitive to Gal antigen-positive xenogeneic grafts and can be effectively utilized for evaluating the α-Gal-mediated immunogenic risk of xenogeneic grafts.

show abstract

Analysis of cytokine functions in graft rejection by gene expression profiles1

Cited by 7 publications

References 30 publications

Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft

Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft

Gene expression changes by amyloid β peptide-stimulated human postmortem brain microglia identify activation of multiple inflammatory processes

GGTA1/iGb3S Double Knockout Mice: Immunological Properties and Immunogenicity Response to Xenogeneic Bone Matrix

Contact Info

Product

Resources

About