A synthetic peptide homologous to the envelope proteins of retroviruses inhibits monocyte-mediated killing by inactivating interleukin 1.
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.
Kleinerman
E S
ES
Department of Cell Biology, University of Texas, M. D. Anderson Hospital and Tumor Institute, Houston 77030.
Lachman
L B
LB
Knowles
R D
RD
Snyderman
R
R
Cianciolo
G J
GJ
D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D017977:Deltaretrovirus / Q000502:physiology; D003864:Depression, Chemical; D015683:Gene Products, gag; D006678:HIV / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D012190:Retroviridae / Q000502:physiology; D012191:Retroviridae Proteins / Q000502:physiology; D015682:Retroviridae Proteins, Oncogenic; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000502:physiology*
D015683:Gene Products, gag; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D010455:Peptides; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C039467:virus structural protein p15; C053692:CKS 17