Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors.

Ikebuchi, Kenji; Wong, Gordon G.; Clark, Steven C.; Hirai, Yoshikatsu; Ogawa, Makio

doi:10.1073/pnas.84.24.9035

Cited by 725 publications

(269 citation statements)

References 37 publications

Supporting

Mentioning

252

Contrasting

Unclassified

Order By: Relevance

“…IL-6 supports HPC proliferation, 28,29,58,59 and we have recently shown it to be a critical regulator of PTH actions in HPC expansion. 13 Because the calvarial organ is composed primarily of stromal osteoblastic cells, the predominant PPR-expressing cell population in the bone marrow, the more significantly increased PTH-induced IL-6 mRNA in Prg4 mutant calvaria suggests that a stromal osteoblastic cell is the target of PTH actions to modulate IL-6 and hematopoietic cells in the marrow of Prg4 mutant mice.…”

Section: Discussionmentioning

confidence: 96%

Proteoglycan 4, a Novel Immunomodulatory Factor, Regulates Parathyroid Hormone Actions on Hematopoietic Cells

Novince¹,

Koh²,

Michalski³

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Proteoglycan 4 (PRG4), a critical protective factor in articular joints, is implicated in hematopoietic progenitor cell expansion and megakaryopoiesis. PRG4 loss-of-function mutations result in camptodactyly-arthropathy-coxa varapericarditis (CACP) syndrome, which is characterized primarily by precocious joint failure. PRG4 was identified as a novel parathyroid hormone (PTH) responsiveness gene in osteoblastic cells in bone, and was investigated as a potential mediator of PTH actions on hematopoiesis. Sixteen-week-old Prg4 ؊/؊ mutant and Prg4 ؉/؉ wild-type mice were treated daily with intermittent PTH (residues 1-34) or vehicle for 6 weeks. At 22 weeks of age, Prg4 mutant mice had increased peripheral blood neutrophils and decreased marrow B220 ؉ (B-lymphocytic) cells, which were normalized by PTH. The PTH-induced increase in marrow Lin ؊ Sca-1 ؉ c-Kit ؉ (hematopoietic progenitor) cells was blunted in mutant mice. Basal and PTHstimulated stromal cell-derived factor-1 (SDF-1) was decreased in mutant mice, suggesting SDF-1 as a candidate regulator of proteoglycan 4 actions on hematopoiesis in vivo. PTH stimulation of IL-6 mRNA was greater in mutant than in wild-type calvaria and bone marrow, suggesting a compensatory mechanism in the PTH-induced increase in marrow hematopoietic progenitor cells. In summary, proteoglycan 4 is a novel PTH-responsive factor regulating immune cells and PTH actions on marrow hematopoietic progenitor cells.

show abstract

Section: Discussionmentioning

confidence: 96%

Proteoglycan 4, a Novel Immunomodulatory Factor, Regulates Parathyroid Hormone Actions on Hematopoietic Cells

Novince¹,

Koh²,

Michalski³

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that IL-6 and IL-11 can amplify the proliferation of immature hematopoietic cells when in combination with stem cell factor and other regulators (18,19). A similar action has been reported for LIF when acting on human cells (20) and LIF, and IL-6 have been reported to amplify the proliferation of purified murine progenitor cells when used in combination with IL-3, GM-CSF, M-CSF, or SCF (21).…”

Section: Discussionmentioning

confidence: 99%

Murine hematopoietic stem cells committed to macrophage/dendritic cell formation: Stimulation by Flk2-ligand with enhancement by regulators using the gp130 receptor chain

Metcalf

1997

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

View full text Add to dashboard Cite

The stimulation by Flk2-ligand (FL) of blast colony formation by murine bone marrow cells was selectively potentiated by the addition of regulators sharing in common the gp130 signaling receptor-leukemia inhibitory factor (LIF), oncostatin M, interleukin 11, or interleukin 6. Recloning of blast colony cells indicated that the majority were progenitor cells committed exclusively to macrophage formation and responding selectively to proliferative stimulation by macrophage colony-stimulating factor. Reculture of blast colony cells initiated by FL plus LIF in cultures containing granulocyte͞macrophage colony-stimulating factor plus tumor necrosis factor ␣ indicated that at least some of the cells were capable of maturation to dendritic cells. The cells forming blast colonies in response to FL plus LIF were unrelated to those forming blast colonies in response to stimulation by stem cell factor and appear to be a distinct subset of mature hematopoietic stem cells.Hematopoietic stem cells can be separated from other murine bone marrow cells by fluorescence-activated cell sorting as a morphologically uniform population, but the population appears to be heterogeneous based on varying proliferative and differentiative potentials. The least mature stem cells exhibit long-term repopulating capacity in vivo and a capacity for self-renewal (1). The most mature stem cells exhibit no capacity for self-renewal but, when stimulated in vitro by stem cell factor (SCF), can form blast colonies composed of progenitor cells committed to differentiation in a number of lineages (2). This action of SCF is strongly enhanced by the addition of colony-stimulating factors (CSFs) or interleukin 6 (IL-6) (3, 4).Flk2-ligand (FL), the ligand for the Flt3͞Flk2 receptor displayed on immature hematopoietic cells, has a relatively weak proliferative action in cultures of marrow cells to stimulate the formation of blast colonies and small numbers of predominantly granulocytic colonies (5). Combinations of FL with other growth factors exhibit enhanced activity in stimulating the proliferation of stem cells to generate progenitor cells and more differentiated progeny (6, 7). Administration of FL to mice increased the formation of dendritic cells (8). In its actions, FL therefore exhibits some features in common with SCF but does differ in other aspects.Leukemia inhibitory factor (LIF) is a pleiotropic factor that can suppress self-generation and induce differentiation in cells of the murine myeloid leukemic cell line, M1 (9). When acting alone in semisolid cultures of murine bone marrow cells, LIF has no observable proliferative action on any hematopoietic population (10).In an analysis of synergistic interactions exhibited by combinations of various growth factors in semisolid cultures of mouse bone marrow cells, it was noted that LIF enhanced colony formation stimulated by FL. The present experiments have analyzed this intriguing example of potentiation of a weak stimulus by addition of a factor with no overt activity and have extended the o...

show abstract

“…Moreover, as shown in Figure 3, patients with detectable serum IL-6 levels had significantly higher plasma fibrinogen levels (4.67 ± 0.65 g 1') than patients without detectable serum IL-6 levels (3.80 ± 0.38 g I-'; P <0.05) and patients with benign lung diseases (3.21 ± 0.70 g -l1; P<0.05). (Ikebuchi et al, 1987;Ishibashi et al, 1989), we studied the possible correlation between serum IL-6 concentrations and blood platelet counts. As shown in Figure 4, there was no significant difference in blood platelet counts between lung cancer patients with detectable (26.5 ± 0.51 x 104 il-1) or undetectable (26.1 ± 0.20 x 104ylh 1) serum IL-6 levels or patients with benign lung diseases (30.1 ± 0.33 x 104 ll-1).…”

Section: Correspondence: H Yanagawamentioning

confidence: 99%

Serum levels of interleukin 6 in patients with lung cancer

Yanagawa

Sone²,

Takahashi³

et al. 1995

Br J Cancer

156

100

View full text Add to dashboard Cite

Japan. SinarySerum interleukin 6 (IL-6) levels were measured in 75 patients with lung cancer and in 20 patients with benign lung diseases. IL-6 was detectable in 29 patients with lung cancer (39%), but was not detectable in any of the patients with benign lung diseases. Serum C-reactive protein levels and plasma fibrinogen levels were significantly higher and serum albumin concentration was significantly lower in lung cancer patients with detectable serum IL-6 levels than in those without detectable serum IL-6 levels and in patients with benign lung diseases. On the other hand, no significant difference was observed in blood platelet counts in these three groups. Moreover, serum IL-6 levels were not significantly different in lung cancer patients with or without clinically demonstrated distant metastasis. These results suggest that IL-6 may be a mediator of various reactions including an inflammatory response in lung cancer patients.Keywords interleukin 6; lung cancer; C-reactive protein; fibrinogen; cachexia; inflammatory response Interleukin 6 (IL-6) is known as a multifunctional cytokine which plays a central role in the host defence mechanism by regulating immune responses, haematopoiesis and acutephase reactions (Kishimoto, 1989). Recently, much attention has been focused on its role in the pathogenesis and progression of various malignancies. It has been reported that IL-6 is an autocrine growth factor for renal cell carcinoma cells (Miki et al., 1989;Koo et al., 1992) and that IL-6 is produced by other non-haematopoietic tumour cells, including bladder carcinoma (Rawle et al., 1989), ovarian carcinoma (Watson et al., 1990) and glioblastoma (Meir et al., 1990). In animal systems, IL-6 appears to have an important role in mediating cancer cachexia (Strassmann et al., 1992). Moreover, elevation of the serum IL-6 level is an adverse prognositic factor in patients with metastatic renal cell carcinoma (Blay et al., 1992). However, there is still little information about the role of IL-6 in vivo in patients with various malignancies.In patients with lung cancer, we have already reported that malignant pleural effusions contain IL-6 (Yanagawa et al., 1992), and we (Mizuno et al., 1994) and others (Matsuguchi et al., 1991) have reported that several lung cancer cell lines constitutively produce IL-6 in vitro. To clarify further the role of IL-6, we examined serum levels of IL-6 in patients with lung cancer. The relationship between serum IL-6 levels and the characteristics of the patients was also analysed. Enzyme immunoassay of IL-6 Serum levels of IL-6 were assayed essentially as described previously (Yanagawa et al., 1992). In brief, microtitre plates (Nunc, Naperville, IL, USA) were coated with anti-IL-6 monoclonal antibody in 100 per well phosphate-buffered saline (PBS). After overnight incubation at 4°C, the wells were blocked with 0.1% bovine serum albumin (BSA) in PBS and washed three times. Volumes of 200 MI of test samples were added to the duplicate wells. The plates were incubated at 37C for 24 h. Aft...

show abstract

Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors.

Cited by 725 publications

References 37 publications

Proteoglycan 4, a Novel Immunomodulatory Factor, Regulates Parathyroid Hormone Actions on Hematopoietic Cells

Proteoglycan 4, a Novel Immunomodulatory Factor, Regulates Parathyroid Hormone Actions on Hematopoietic Cells

Murine hematopoietic stem cells committed to macrophage/dendritic cell formation: Stimulation by Flk2-ligand with enhancement by regulators using the gp130 receptor chain

Serum levels of interleukin 6 in patients with lung cancer

Contact Info

Product

Resources

About