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Post‐transcriptional regulation of C‐C motif chemokine ligand 2 expression by ribosomal protein L22 during LPS‐mediated inflammation
Author(s) -
Das Anindhya Sundar,
Basu Anandita,
Kumar Ravi,
Borah Pallab Kumar,
Bakshi Subhojit,
Sharma Manoj,
Duary Raj Kumar,
Ray Partho Sarothi,
Mukhopadhyay Rupak
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15362
Subject(s) - chemokine , monocyte , inflammation , ccl2 , downregulation and upregulation , biology , microbiology and biotechnology , transcriptional regulation , ribosomal protein , ccr2 , chemistry , transcription factor , chemokine receptor , immunology , gene , biochemistry , ribosome , rna
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 ).