PMID- 2207333
OWN - NLM
STAT- MEDLINE
DCOM- 19901119
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 76
IP  - 8
DP  - 1990 Oct 15
TI  - Recombinant C5a stimulates transcription rather than translation of interleukin-1 
      (IL-1) and tumor necrosis factor: translational signal provided by 
      lipopolysaccharide or IL-1 itself.
PG  - 1631-8
AB  - We investigated the effects of recombinant C5a (rC5a) on gene expression and 
      synthesis of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) in 
      fresh human peripheral blood mononuclear cells (PBMC). Total (cell-associated and 
      secreted) cytokine synthesis was measured. In the strict absence of endotoxin 
      (lipopolysaccharide [LPS]), rC5a resulted in a small but statistically 
      insignificant increase in immunoreactive IL-1 beta and TNF, as well as in IL-1 
      and IL-6 bioactivity. On the other hand, rC5a induced marked transcriptional 
      activation of IL-1 beta and TNF in a dose-dependent fashion with an optimal 
      concentration of 50 ng/mL. The rC5a-induced cytokine messenger RNA (mRNA) was not 
      spontaneously translated into protein. At 50 ng/mL, rC5a induced the same levels 
      of mRNA for IL-1 beta and TNF as 1 ng/mL of LPS, whereas LPS induced 12 times 
      more IL-1 beta protein and 70 times more TNF protein than rC5a alone. The 
      C5a-induced mRNA half-life was the same as that induced by LPS. 
      Formyl-Meth-Leu-Phe (fMLP) did not induce cytokine transcription. Pretreatment 
      with rC5a enhanced cytokine synthesis induced by other stimuli. After 2 hours of 
      preincubation with rC5a, PBMC synthesized 3 to 10 times more IL-1 beta and TNF on 
      subsequent stimulation by LPS or IL-1 itself. We conclude that rC5a provides 
      primarily a transcriptional but not translational signal for IL-1 beta and TNF; 
      the half-life of the untranslated mRNA is the same as that of translated message; 
      rC5a-induced transcription upregulates PBMC for enhanced synthesis of these 
      cytokines; and a translational signal can be provided by LPS or IL-1 itself.
FAU - Schindler, R
AU  - Schindler R
AD  - Department of Medicine, Tufts University School of Medicine, Boston, MA.
FAU - Gelfand, J A
AU  - Gelfand JA
FAU - Dinarello, C A
AU  - Dinarello CA
LA  - eng
GR  - AI 15614/AI/NIAID NIH HHS/United States
GR  - GM-21700/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 80295-54-1 (Complement C5a)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Complement C5a/*pharmacology
MH  - Gene Expression
MH  - Humans
MH  - Interleukin-1/biosynthesis/*genetics/pharmacology
MH  - Lipopolysaccharides/*pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - *Protein Biosynthesis
MH  - RNA, Messenger/biosynthesis
MH  - Recombinant Proteins/pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - *Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/biosynthesis/*genetics
EDAT- 1990/10/15 00:00
MHDA- 1990/10/15 00:01
CRDT- 1990/10/15 00:00
PHST- 1990/10/15 00:00 [pubmed]
PHST- 1990/10/15 00:01 [medline]
PHST- 1990/10/15 00:00 [entrez]
AID - S0006-4971(20)75237-7 [pii]
PST - ppublish
SO  - Blood. 1990 Oct 15;76(8):1631-8.