Human IFN-gamma production is inhibited by a synthetic peptide homologous to retroviral envelope protein.
A synthetic 17 amino acid peptide (CKS-17) homologous to a highly conserved region of human and animal retroviral transmembrane proteins was investigated for its influence on the in vitro production of IFN-gamma from human peripheral mononuclear cells. The results showed that CKS-17 coupled to a carrier protein, BSA, inhibited production of IFN-gamma in a dose-dependent manner. Controls, consisting of BSA, which had undergone the coupling procedure or neurotensin coupled to BSA in an identical manner as CKS-17, showed no such inhibition. Reduction in IFN-gamma production could not be attributed to decreased viability of cells, delay of IFN-gamma production or to involvement of suppressor cells. Moreover, inhibition of IFN-gamma production was not related to the inhibition of DNA synthesis. The inhibition appeared to be a direct effect of CKS-17 on IFN-gamma-producing cells. Kinetic studies revealed that this suppression occurred when CKS-17 was introduced to the culture concurrent with or within 48 h after introduction of IFN inducers. Preincubation experiments showed that the presence of CKS-17 in the culture medium was not necessary to exert its inhibitory effect. These results suggest that a portion of retroviral envelope proteins possess important immunomodulatory actions.
Ogasawara
M
M
All Children's Hospital, St. Petersburg, FL 33701.
Cianciolo
G J
GJ
Snyderman
R
R
Mitani
M
M
Good
R A
RA
Day
N K
NK
D000595:Amino Acid Sequence; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012191:Retroviridae Proteins / Q000235:genetics / Q000494:pharmacology*; D012689:Sequence Homology, Nucleic Acid; D012710:Serum Albumin, Bovine; D013211:Staphylococcus aureus; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013936:Thymidine / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000494:pharmacology*
D004768:Enterotoxins; D007166:Immunosuppressive Agents; D010455:Peptides; D011500:Protein Synthesis Inhibitors; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D012710:Serum Albumin, Bovine; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma; D013936:Thymidine