ABSTRACT
Immune cells express powerful and harmful effectors that require tight regulation. Heterotrimeric G proteins are critical mediators in translating extracellular signals into cell responses, which need a fine-tuned regulation for the control of cell activation. Regulator of G-protein signalling 16 (RGS16) has been identified as a key factor of G protein-mediated activation in lymphocytes, modulating inflammatory and survival responses of various cell types. However, data about the expression of this regulatory protein in monocytes are scarce, and it has remained unclear whether activation and migration of these cells are regulated by RGS16. In this study, the impact of RGS16 on the production of inflammatory cytokines by activated human monocytes was investigated in vitro using the human promonocytic cell line THP-1 as a model. Gain and loss of function experiments showed that RGS16 overexpression reduces the expression of pro-inflammatory cytokines IL-1ß, IL-6, IL-8 and TNFα, while RGS16 knockdown by RNAi upregulates IL-1ß, IL-6 and TNFα but not IL-8. RGS16 knockdown was also shown to enhance Pam3-mediated induction of the anti-inflammatory cytokine IL-10. Our results indicate that RGS16 restricts the activation-induced pro-inflammatory profile in myeloid cells.
Subject(s)
Inflammation/immunology , Lymphocyte Activation/immunology , Macrophages/immunology , Monocytes/immunology , RGS Proteins/immunology , Animals , Bone Marrow Cells , Cell Line , Humans , Interleukin-10/biosynthesis , Interleukin-1beta/biosynthesis , Interleukin-6/biosynthesis , Interleukin-8/biosynthesis , Lipopeptides/pharmacology , Mice , Mice, Inbred C57BL , Mice, Knockout , RGS Proteins/biosynthesis , RGS Proteins/genetics , RNA Interference , RNA, Small Interfering , Toll-Like Receptor 2/agonists , Tumor Necrosis Factor-alpha/biosynthesisSubject(s)
Birds , Conservation of Natural Resources , Ecosystem , Food Chain , Alaska , Animals , Climate , Eutrophication , Oceans and SeasABSTRACT
The recently deciphered sequence of the human mitochondrial genome is analyzed in the light of an archigenetic hypothesis, according to which mitochondria are derived neither from pro- nor eukaryotes but from more primitive organisms. The possibility that animal mitochondria have only one gene both for elongator and initiator methionine tRNA is supported but C-A pair forming cytosine in the anticodon of these tRNAs is considered to be unmodified. The evolution of the gene and of the codon reading pattern of the methionine tRNA is discussed.
Subject(s)
Biological Evolution , DNA, Mitochondrial/genetics , Peptide Elongation Factors/genetics , Peptide Initiation Factors/genetics , RNA, Transfer, Amino Acyl/genetics , Animals , Anticodon/genetics , Bacteria/genetics , Base Sequence , Codon/genetics , Fungi/genetics , Humans , Plants/genetics , RNA, Bacterial/genetics , RNA, Fungal/geneticsABSTRACT
220 nucleotide sequences of tRNAs were investigated to elucidate the frequency of appearance of C-A pairs in their main two-stranded regions, in the positions 26--44 and 15--48. It was supposed, that in the formation of C-A pairs on antiparallel polynucleotide chains the atomic groups--N4-H and -N3 of cytosine make up H-bonds with the groups N7- and H-N6--of adenine. On parallel chains, H-bonds, probably, form -N6-H and --N1 groups of adenine with N3- and H-N4--of cytosine. The calculation results predicted a significant energy of ineraction between cytosine and adenine. By the investigation of the molecular models it was shown that the formation of H-bonded C-A pairs requires considerable changes of conformation in rebosephosphate chains. In addition a theoretical analysis revealed the possibility of formation of C-A pairs at the wobble-position of codon-anticodon complex. The significance of this nucleotide pair in the processes of genetic coding proved to depend on the stability of the codon-anticodon complex, modification of cytosine 34 and structural features of the distant regions of the tRNA.
