TLR2 signaling by Mycobacterium tuberculosis 19-kDa lipoprotein (LpqH) inhibits IFN-gamma-induced expression of CIITA by macrophages. Microarray analysis, quantitative RT-PCR, and Western blots showed that LpqH induced C/EBPbeta and C/EBPdelta in kinetic correlation with inhibition of CIITA expression. Of the C/EBPbeta isoforms, liver inhibitory protein (LIP) was notably induced and liver-activating protein was increased by LpqH. Putative C/EBP binding sites were identified in CIITA promoters I and IV (pI and pIV). LpqH induced binding of C/EBPbeta (LIP and liver-activating protein) to biotinylated oligodeoxynucleotide containing the pI or pIV binding sites, and chromatin immunoprecipitation showed that LpqH induced binding of C/EBPbeta and C/EBPdelta to endogenous CIITA pI and pIV. Constitutive expression of C/EBPbeta LIP inhibited IFN-gamma-induced CIITA expression in transfected cells. In summary, LpqH induced expression of C/EBPbeta and C/EBPdelta, and their binding to CIITA pI and pIV, in correlation with inhibition of IFN-gamma-induced expression of CIITA in macrophages, suggesting a role for C/EBP as a novel regulator of CIITA expression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631233 | PMC |
| http://dx.doi.org/10.4049/jimmunol.179.10.6910 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia.
Haematologica
December 2024
Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen.
Acute myeloid leukemia (AML) remains challenging to treat, which in part relates to genetic heterogeneity of the disease, to the protective tumor microenvironment driving resistance to therapy, and also to immune evasion characteristics of leukemic cells. Targeting epigenetic programs in AML provides an attractive opportunity to impair long-term proliferation and induce differentiation. The novel inhibitor JNJ- 75276617 (bleximenib) targets the menin-KMT2A interaction and provides preclinical efficacy in AML (Kwon et al1).
View Article and Find Full Text PDFMeta-analyses uncover the genetic architecture of Idiopathic Inflammatory Myopathies.
Arthritis Rheumatol
December 2024
Institute for Clinical and Translational Research, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Objective: Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra-muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.
View Article and Find Full Text PDFExploring immune gene expression and potential regulatory mechanisms in anaplastic thyroid carcinoma using a combination of single-cell and bulk RNA sequencing data.
Comput Biol Chem
December 2024
Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, China; Department of Thyroid Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Hangzhou, Zhejiang 310022, China. Electronic address:
Thyroid cancer includes papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC). While PTC has an excellent prognosis, ATC has a dismal prognosis, necessitating the identification of novel targets in ATC to aid in ATC diagnosis and treatment. Therefore, we analyzed ATC single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data from the Gene Expression Omnibus (GEO), retrieved immune-related genes from the ImmPort database, and identified differentially expressed immune genes within single-cell subgroups.
View Article and Find Full Text PDFNon-Immune-Mediated, p27-Associated, Growth Inhibition of Glioblastoma by Class-II-Transactivator (CIITA).
Cells
November 2024
Department of Translational Neuroscience, University Medical Center Utrecht (UMCU) Brain Center, Utrecht University, 3584 CX Utrecht, The Netherlands.
Background: Previous works have shown that the expression of Class-II-Transactivator (CIITA) in tumor cells reduces the growth of glioblastoma (GB) in animal models, but immune effects cannot solely explain this. Here, we searched for immune-independent effects of CIITA on the proliferation of GB.
Methods: Murine GL261 and human U87, GM2 and GM3 malignant glioma cells were transfected with CIITA.
ZBTB48 is a priming factor regulating B-cell-specific CIITA expression.
EMBO J
December 2024
Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore, Singapore.
The class-II transactivator (CIITA) is the master regulator of MHC class-II gene expression and hence the adaptive immune response. Three cell type-specific promoters (pI, pIII, and pIV) are involved in the regulation of CIITA expression, which can be induced by IFN-γ in non-immune cells. While key regulatory elements have been identified within these promoters, our understanding of the transcription factors regulating CIITA expression is incomplete.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!