A synthetic peptide homologous to the envelope proteins of retroviruses inhibits monocyte-mediated killing by inactivating interleukin 1.

Abstract

The synthetic peptide CKS-17 has homology to a highly conserved region of the immunosuppressive retroviral envelope protein P15E, to envelope proteins of HTLV I, II, III, and to that encoded by an endogeneous C-type human retroviral DNA. CKS-17 inhibits the immune response of lymphocytes and the respiratory burst of human monocytes. Because P15E-related antigens are present in human malignant cell lines and cancerous effusions, we sought to determine the effect of CKS-17 on monocyte-mediated tumor cell lysis. Lysis of A375 tumor cells by lymphokine or lipopolysaccharide-activated human monocytes was inhibited by 10 microM CKS-17 (control, 79%; CKS-17-treated, 19%). Another synthesized peptide, CS-2, which has partial homology to CKS-17, failed to block monocyte-mediated killing. Thus, the inhibition by CKS-17 appeared to be specific. Because interleukin 1 (IL-1) is a cytocidal factor produced by activated monocytes, we also investigated the effect of CKS-17 on IL-1 production by monocytes and on direct IL-1-mediated cytotoxicity. CKS-17 did not block production or secretion of IL-1 by lipopolysaccharide- or interferon-gamma-activated monocytes. However, the direct cytocidal activity of both recombinant IL-1 alpha and IL-1 beta against A375 tumor cells was blocked by CKS-17. The cytotoxic activity of IL-1 was inhibited by CKS-17 if (a) IL-1 was preincubated with CKS-17 for 1 hr at 37 degrees C or (b) the A375 cells were incubated with CKS-17 for 1 hr prior to the addition of IL-1. CKS-17 also blocked IL-1-induced proliferation of murine thymocytes, the D10 T cell line, and an IL-1-responsive astrocytoma cell line. These data suggest that CKS-17 may be a potent inhibitor of IL-1.

• Authors: E S Kleinerman, L B Lachman, R D Knowles, R Snyderman, G J Cianciolo
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 139 Issue 7 Pg. 2329-37 (Oct 01 1987) ISSN: 0022-1767 [Print] United States
• PMID: 2821111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Gene Products, gag
• Intercellular Signaling Peptides and Proteins
• Interleukin-1
• Peptides
• Retroviridae Proteins
• Retroviridae Proteins, Oncogenic
• Viral Envelope Proteins
• virus structural protein p15
• CKS 17

Topics

• Cytotoxicity, Immunologic (drug effects)
• Deltaretrovirus (physiology)
• Depression, Chemical
• Gene Products, gag
• HIV (physiology)
• Intercellular Signaling Peptides and Proteins
• Interleukin-1 (antagonists & inhibitors, metabolism)
• Leukocytes, Mononuclear (drug effects, immunology)
• Peptides (chemical synthesis, pharmacology)
• Retroviridae (physiology)
• Retroviridae Proteins (physiology)
• Retroviridae Proteins, Oncogenic
• Sequence Homology, Nucleic Acid
• Tumor Cells, Cultured
• Viral Envelope Proteins (physiology)