The differential production of three forms of IL-1 receptor antagonist by human neutrophils and monocytes. 1998

M Malyak, and M F Smith, and A A Abel, and K R Hance, and W P Arend
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.

IL-1R antagonist (IL-1Ra) exists as three well-characterized isoforms. The 17-kDa secretory IL-1Ra (sIL-1Ra) and 18-kDa intracellular IL-1Ra (icIL-1RaI) arise by alternative transcription of the same IL-1Ra gene. The recently described 16-kDa intracellular IL-1Ra (icIL-1RaII) is formed by alternative translation initiation of sIL-1Ra mRNA. Transcription and translation of IL-1Ra isoforms were examined in LPS-stimulated human neutrophils and PBMC using RT-PCR, ELISA, and Western blot analysis. LPS stimulation of neutrophils resulted in elevated sIL-1Ra mRNA levels by 1 h, whereas icIL-1RaI mRNA remained undetectable through 22 h of culture. Extracellular glycosylated sIL-1Ra protein and intracellular icIL-1RaII were observed in LPS-stimulated neutrophils by 3 h of culture; no icIL-1RaI protein was detected by immunoblot. LPS stimulation of PBMC resulted in elevated sIL-1Ra mRNA levels by 1 h and detectable icIL-1RaI mRNA at 8 h of culture. LPS-stimulated PBMC demonstrated extracellular glycosylated sIL-1Ra protein and intracellular icIL-1RaII within 3 h of stimulation, whereas detection of icIL-1RaI protein was delayed until 15 h of culture. Subcellular localization experiments established that both icIL-1RaI and icIL-1RaII were present primarily within the cytoplasmic compartment, as expected by their lack of a signal peptide. These results demonstrate that although both LPS-stimulated neutrophils and PBMC synthesize sIL-1Ra and icIL-1RaII, only PBMC transcribe and translate icIL-1RaI. Furthermore, sIL-Ra transcription and translation (and translation of icIL-1RaII) are early events, whereas icIL-1RaI transcription in PBMC is delayed.

UI MeSH Term Description Entries
D007424 Intracellular Fluid The fluid inside CELLS. Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D007536 Isomerism The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Isomerisms
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012795 Sialoglycoproteins Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities. Polysialoglycoprotein,Sialoglycopeptide,Sialoglycopeptides,Sialoglycoprotein,Sialoprotein,Sialoproteins,Polysialoglycoproteins
D013347 Subcellular Fractions Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163) Fraction, Subcellular,Fractions, Subcellular,Subcellular Fraction

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