The hemoregulatory peptide pEEDCK may inhibit stem cell proliferation via hydropathic binding to antisense sequence motifs in interleukin-11 and other growth factors.

In undisturbed bone marrow, most hemopoietic stem cells are nonproliferating despite the presence of multiple growth factors. Endogenous inhibitory factors are responsible for maintenance of this quiescence. Previously we sequenced and synthesized the inhibitory pentapeptide pGlu-Glu-Asp-Cys-Lys (pEEDCK), which originally derives from granulocytes, and investigated the role of this peptide in stem cell quiescence.

Activated granulocytes oxidize the endogenous stem cell inhibitory peptide pGlu-Glu-Asp-Cys-Lys (pEEDCK) to the stimulatory dimer: a redox-mediated mechanism for demand-induced hematopoietic regulation.

We have previously shown that the pentapeptide pGlu-Glu-Asp-Cys-Lys (pEEDCK), which is associated with mature leukocytes, maintains pluripotent hematopoietic stem cells (colony-forming units-spleen [CFU-S]) in a quiescent state under physiological conditions. It is also known that its oxidation product, the disulfide-bonded homodimer (pEEDCK)2, is a growth factor for CFU-S in vivo. In this paper we report on the combined actions of the monomer and dimer in inducing rapid changes in stem cell proliferation in vivo.

Stem cell stimulation in vitro by the dekapeptide (pEEDCK)2: a single-factor alternative for multifactor cocktails.

Insertion of foreign genes into cellular DNA requires (at least one round of) DNA replication. Since hemopoietic stem cells do not divide rapidly, numerous semi-empirically designed multifactor cocktails have been used to stimulate them. In an attempt to find an alternative to this approach we have investigated the effects of the stem cell stimulatory peptide (pGlu-Glu-Asp-Glys-Lys)2, (pEEDCK)2, on progenitor output in murine long-term bone marrow cultures (LTBMC).

Proteolytic enzymes and amylase induce cytokine production in human peripheral blood mononuclear cells in vitro.

In vitro treatment of human peripheral blood mononuclear cells (PBMNC) with proteolytic enzymes (bromelain, papain) and amylase leads to the production of large amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6) in a time and dose dependent manner. Increased TNF-alpha and IL-6 production was already found after 4-6 hours of incubation, and plateau levels were reached after 12-16 hours. Plateau levels up to 1500 pg TNF-alpha/ml/10(6) PBMNC, 13000 pg IL-1 beta/ml/10(6) PBMNC, and 23000 pg IL-6/ml/10(6) PBMNC were observed.

Cytokine synthesis in human peripheral blood mononuclear cells after oral administration of polyenzyme preparations.

Pharmaceutical preparations containing mixtures of various proteolytic and nonproteolytic enzymes have been suggested for use in the treatment of malignant diseases. However, the mode of action of such preparations was not clear. We have shown before that intact bromelain, papain or amylase, which are components of a commercial polyenzyme preparation, induce cytokine production in peripheral blood mononuclear cells in vitro.