Differential Modulation of Th1- and Th2-Related Cytokine mRNA Expression by a Synthetic Peptide Homologous to a Conserved Domain within Retroviral Envelope Protein

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-04, Vol.92 (8), p.3611-3615
• Main Authors: Haraguchi, Soichi, Good, Robert A., James-Yarish, Michelle, Cianciolo, George J., Day, Noorbibi K.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acid Sequence; B lymphocytes; Base Sequence; Cancer; Cellular biology; Cytokines; Cytokines - biosynthesis; Cytokines - genetics; Dimers; Gene Expression Regulation; HIV; Humans; Immunity (Disease); Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Interleukins - biosynthesis; Interleukins - genetics; Messenger RNA; Molecular Sequence Data; Peptides - pharmacology; Polymerase chain reaction; Retroviridae; Retroviridae Proteins - pharmacology; Reverse transcriptase polymerase chain reaction; RNA, Messenger - analysis; Stimulants; T lymphocytes; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; Viral Envelope Proteins - pharmacology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.8.3611

The influence of a synthetic retroviral peptide, CKS-17, on T helper type 1 (Th1)- or Th2-related cytokines was investigated in human blood mononuclear cells. Cells were stimulated with staphylococcal enterotoxin A, anti-CD3 plus anti-CD28 monoclonal antibodies, or lipopolysaccharide to induce cytokine mRNA. mRNA was detected by a reverse transcription-polymerase chain reaction or Northern blot analysis. CKS-17 down-regulated stimulant-induced mRNA accumulation for interferon γ (IFN-γ), interleukin (IL)-2, and p40 heavy and p35 light chains of IL-12, a cytokine that mediates development of Th1 response. CKS-17 up-regulated stimulant-induced mRNA accumulation of IL-10 and did not suppress Th2-related cytokine (IL-4, IL-5, IL-6, or IL-13) mRNA expression. A reverse sequence of CKS-17 peptide, used as a control, showed no such action. Anti-human IL-10 monoclonal antibody blocked ability of CKS-17 to inhibit mRNA accumulation for IFN-γ but not the CKS-17 suppressive activity of IL-12 p40 heavy chain mRNA. Thus, CKS-17-mediated suppression of IFN-γ mRNA expression is dependent upon augmentation of IL-10 production by CKS-17. This conserved component of several retroviral envelope proteins, CKS-17, may act as an immunomodulatory epitope responsible for cytokine dysregulation that leads to suppression of cellular immunity.