Effect of anticancer agents neothramycin, aclacinomycin, FK-565 and FK-156 on the release of interleukin-2 and interleukin-1 in vitro

Ahmed, Khalid; Turk, J.L.

doi:10.1007/bf00199107

Cited by 22 publications

(7 citation statements)

References 19 publications

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“…MDP and several other adjuvant-active analogs induce high levels of membranebound IL-1 in mouse peritoneal macrophages; in contrast, adjuvant-inactive analogs, such as MDP containing D-Ala, are unable to trigger IL-1 production (16). FK-565 and FK-156 also induce the release of IL-1 from lipopolysaccharide-stimulated rat peritoneal exudate cells (29). In keeping with this pattern,…”

Section: Discussionsupporting

confidence: 65%

Bordetella pertussis tracheal cytotoxin and other muramyl peptides: distinct structure-activity relationships for respiratory epithelial cytopathology.

Luker

Collier

Kolodziej

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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Tracheal cytotoxin (TCT) is a disaccharidetetrapeptide released by Bordetella pertussis, the causative agent of pertussis (whooping cough). We have previously determined the structure of TCT to be GIcNAc-1,6-anhydroMurNAc-L-Ala-y-D-Glu-meso-A2pm-D-Ala, where MurNAc = N-acetylmuramic acid and A2pm = diaminopimelic acid. Purified TCT reproduces the respiratory cytopathology observed during pertussis, including ciliostasis and extrusion of ciliated cells. We have tested structural analogs of TCT for their ability to reproduce native TCT toxicity in explanted hamster tracheal tissue and hamster trachea epithelial (HTE) cell cultures. Other investigators have evaluated many of these analogs, which are muramyl or desmuramyl peptides, for muramyl peptide activities such as immunopotentiation, induction of slow-wave sleep, and pyrogenicity. Four desmuramyl peptides were produced in our laboratory from B. pertussis peptidoglycan or by chemical synthesis, including unusual peptides containing a-aminopimelic acid in place of A2pm. Based on the relative ability of compounds to inhibit DNA synthesis in HTE cells, truncated analogs lacking A2pm entirely or lacking only the side-chain amine or carboxyl group of A2pm were less active than TCT by a factor of at least 1000. All active analogs included a native or near-native peptide moiety, independent of the presence, absence, or substitution of the sugar moiety. We conclude that the structural requirements for TCT toxicity differ considerably from those for most other muramyl peptide activities, in that the disaccharide moiety is irrelevant for toxicity and both the free amino and carboxyl groups of the A2pm side chain are required for activity.Tracheal cytotoxin (TCT) is a low molecular weight glycopeptide released during logarithmic-phase growth of Bordetella pertussis. It is the only B. pertussis product that reproduces the respiratory cytopathology observed during pertussis (whooping cough) (1). This pathology includes ciliostasis and specific extrusion of ciliated cells from the respiratory epithelium. In the absence of ciliary activity, coughing becomes the only way to clear the airways of accumulating mucus, bacteria, and inflammatory debris. Thus, TCT-mediated destruction of ciliated cells may trigger the violent coughing episodes symptomatic of pertussis. In addition, the absence of a ciliary clearance mechanism predisposes patients to secondary pulmonary infections, the primary cause of pertussis mortality (2).We have previously reported the purification of TCT by reversed-phase HPLC (RP-HPLC) and determined its structure by fast atom bombardment (FAB)-MS to be GlcNAc-1,6-anhydro-MurNAc-L-Ala-y-D-Glu-meso-A2pm-D-Ala (Fig. 1) (3), where MurNAc is N-acetylmuramic acid and A2pm is diaminopimelic acid. TCT belongs to a family of compounds known as muramyl peptides, which have many biological activities including adjuvanticity, somnogenicity, and pyrogenicity (4-6). Naturally occurring muramyl peptides are of bacterial origin; they are fragments of peptidoglycan, t...

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Section: Discussionsupporting

confidence: 65%

Bordetella pertussis tracheal cytotoxin and other muramyl peptides: distinct structure-activity relationships for respiratory epithelial cytopathology.

Luker

Collier

Kolodziej

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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“…They are known to increase resistance to microbial infections and are associated with inereased tumoricidal activity of macrophage [15,13]. Increased T N F production in vitro by FK565 correlates with out previous report of enhancement of IL-1 in vitro by this drug [4]. In this study FK156 did not significantly alter the release of T N F although it enhanced IL-1 release in vitro in out previous work.…”

Section: Discussionsupporting

confidence: 91%

“…We have shown an enhancement of the release of IL-2 in vitro and in vivo by Adriamycin and bleomycin, and inhibition of IL-2 by vincristine, vinblastine and cyclophosphamide under similar conditions [1][2][3]5]. We have also reported that the release of IL-1 is increased in vitro by Adriamycin, bleomycin, and the experimental peptides FK565 and FK156 [2][3][4].…”

Section: Introductionmentioning

confidence: 73%

Effect of anticancer drugs on the release of tumour necrosis factor in vitro

Hasan

Ahmed

Turk

1990

Cancer Immunol Immunother

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The anticancer drugs Adriamycin, bleomycin, vincristine, 4-hydroperoxycyclophosphamide, FK156 and FK565 and the immunosuppressive drug cyclosporin-A were tested for their effect on lipopolysaccharide-induced tumour necrosis factor-alpha (TNF) release from rat peritoneal exudate cells in vitro. FK565 resulted in a marked enhancement of TNF release when added to cultures at doses of 1 microgram/ml and 10 micrograms/ml. However, FK156, Adriamycin, bleomycin, 4-hydroperoxycyclophosphamide, vincristine and cyclosporin A did not affect the release of TNF under the same conditions. Puromycin inhibited the release of TNF in the same system at non-cytotoxic doses of 1 microgram/ml and 10 micrograms/ml.

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“…These compounds did not alter the release of IL-6 in these experiments. In earlier studies these peptides had increased the release of IL-1, and FK565 induced enhanced TNF release from rat macrophages [2,15], whilst IL-2 release from spleen cells was reduced by the peptides [2]. Interferon y and IL-3 have not been affected by these compounds [4,14].…”

Section: Discussionmentioning

confidence: 88%

Effect of anticancer drugs on the release of interleukin-6 in vitro

Hasan

Blaney

Turk

1992

Cancer Immunol Immunother

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This study investigates the effects of anticancer drugs and immunomodulating agents on the release of interleukin-6 (IL-6) from lipopolysaccharide-stimulated human peripheral blood mononuclear leucocytes in vitro. The addition of non-cytotoxic concentrations of Adriamycin (doxorubicin), vincristine and 4-OOH-cyclophosphamide (the in vitro active analogue of cyclophosphamide) resulted in suppression of IL-6 release. The drugs bleomycin, FK156 [D-lactoyl-L-alanyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(L)-g lycine], FK565 [heptanoyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alan ine] and the immunosuppressive agent cyclosporin A did not alter the release of IL-6 in the same experimental system.

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Effect of anticancer agents neothramycin, aclacinomycin, FK-565 and FK-156 on the release of interleukin-2 and interleukin-1 in vitro

Cited by 22 publications

References 19 publications

Bordetella pertussis tracheal cytotoxin and other muramyl peptides: distinct structure-activity relationships for respiratory epithelial cytopathology.

Bordetella pertussis tracheal cytotoxin and other muramyl peptides: distinct structure-activity relationships for respiratory epithelial cytopathology.

Effect of anticancer drugs on the release of tumour necrosis factor in vitro

Effect of anticancer drugs on the release of interleukin-6 in vitro

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