Transcriptional Modification and Potential Intracellular Signaling Mechanisms in Human Macrophages Primed by Interferon-γ.
10.19746/j.cnki.issn.1009-2137.2022.05.045
- Author:
Bei LIU
1
;
Hong-Hao GAO
2
;
Li CHENG
2
;
Jia-Le ZHANG
3
;
Yan-Xin DONG
3
;
Shun XIE
3
;
Wen-Rong HUANG
4
;
Shun-Zong YUAN
5
Author Information
1. The PLA 307 Clinical College of Anhui Medical University, Beijing 100071, China.
2. Section 4, Department of Hematology, The Fifth Medical Center of PLA General Hospital, Beijing 100071, China.
3. Department of Thoracic Surgery, The Sixth Medical Center of PLA General Hospital, Beijing 100048, China.
4. Section 4, Department of Hematology, The Fifth Medical Center of PLA General Hospital, Beijing 100071, China,E-mail: huangwr301@163.com.
5. The PLA 307 Clinical College of Anhui Medical University, Beijing 100071, China,Section 4, Department of Hematology, The Fifth Medical Center of PLA General Hospital, Beijing 100071, China.
- Publication Type:Journal Article
- Keywords:
IFN-γ;
intracellular signaling;
transcriptome;
uman macrophagesh
- MeSH:
Apolipoprotein L1/pharmacology*;
Humans;
Interferon-gamma/pharmacology*;
Macrophages/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
Signal Transduction
- From:
Journal of Experimental Hematology
2022;30(5):1590-1596
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the transcriptional gene expression profile up-regulated in human macrophages stimulated by interferon-γ (IFN-γ) and the underlying intracellular signaling mechanisms.
METHODS:RNA-seq was used to sequence and compare the differential gene expression profiles of human macrophage cell line U937 before and after IFN-γ stimulation, and the significantly up-regulated genes were screened out, which were verified by fluorescence-based real-time quantitative polymerase chain reaction (qPCR) in U937 and THP1 cell lines, respectively. JAK/STAT, MAPK/ERK and PI3K/AKT pathway inhibitors were added to simultaneously to the cultured U937 cells upon IFN-γ priming to detect their effects on the expressions of the up-regulated genes to explore the key regulatory mechanisms.
RESULTS:RNA-seq and qPCR results showed that, the well-recognized chemokines CXCL9, CXCL10 and CXCL11, the APOL family including APOL1, APOL2, APOL3, APOL4, APOL6 and GBP family GBP1, GBP2, GBP3, GBP4 and GBP5 as well were significantly up-regulated in IFN-γ-stimulated U937 cells. JAK/STAT3 pathway inhibitor inhibited the upregulation of APOL1, APOL4, GBP1, GBP4 and GBP5 genes induced by IFN-γ, while MAPK/ERK pathway inhibitor inhibited the upregulation of CXCL10 gene. PI3K/AKT pathway inhibitor inhibited the upregulation of APOL1,APOL4, APOL6, GBP1 and GBP5 genes induced by IFN-γ, all three signal pathway inhibitors could inhibit the upregulation of CXCL9 gene, and none of them could inhibit the upregulation of APOL3 gene.
CONCLUSION:Upon IFN-γ stimulation, some family molecules of APOL and GBP in macrophages are significantly up-regulated, and PI3K/AKT, JAK/STAT3 and MAPK/ERK pathways have positive regulation on their expressions, respectively.
