Post-transcriptional regulation of C-C motif chemokine ligand 2 expression by ribosomal protein L22 during LPS-mediated inflammation

Autor: Subhojit Bakshi, Pallab Kumar Borah, Anandita Basu, Ravi Kumar, Partho Sarothi Ray, Manoj Sharma, Raj Kumar Duary, Anindhya Sundar Das, Rupak Mukhopadhyay
Rok vydání: 2019
Předmět:
0301 basic medicine
Lipopolysaccharides
Models
Molecular
Ribosomal Proteins
Chemokine
Protein Conformation
THP-1 Cells
RNA Stability
Active Transport
Cell Nucleus
Inflammation
CCL2
Biochemistry
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Ribosomal protein
Cell Movement
Large ribosomal subunit
Sequence Homology
Nucleic Acid
Protein Interaction Mapping
medicine
Humans
RNA
Messenger
Molecular Biology
Post-transcriptional regulation
Chemokine CCL2
biology
Base Sequence
Chemistry
Monocyte
RNA-Binding Proteins
Cell Biology
Cell biology
Neoplasm Proteins
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
biology.protein
MCF-7 Cells
Trans-Activators
medicine.symptom
CRISPR-Cas Systems
5' Untranslated Regions
Protein Processing
Post-Translational
Sequence Alignment
RNA Helicases
Zdroj: The FEBS journalReferences. 287(17)
ISSN: 1742-4658
Popis: Monocyte infiltration to the site of pathogenic invasion is critical for inflammatory response and host defence. However, this process demands precise regulation as uncontrolled migration of monocytes to the site delays resolution of inflammation and ultimately promotes chronic inflammation. C-C motif chemokine ligand 2 (CCL2) plays a key role in monocyte migration, and hence, its expression should be tightly regulated. Here, we report a post-transcriptional regulation of CCL2 involving the large ribosomal subunit protein L22 (RPL22) in LPS-activated, differentiated THP-1 cells. Early events following LPS treatment include transcriptional upregulation of RPL22 and its nuclear accumulation. The protein binds to the first 20 nt sequence of the 5'UTR of ccl2 mRNA. Simultaneous nuclear translocation of up-frameshift-1 protein and its interaction with RPL22 results in cytoplasmic degradation of the ccl2 mRNA at a later stage. Removal of RPL22 from cells results in increased expression of CCL2 in response to LPS causing disproportionate migration of monocytes. We propose that post-transcriptional regulation of CCL2 by RPL22 fine-tunes monocyte infiltration during a pathogenic insult and maintains homeostasis of the immune response critical to resolution of inflammation. DATABASES: Microarray data are available in NCBI GEO database (Accession No GSE126525).
Databáze: OpenAIRE
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