scholarly journals Macrophages and Immune Responses in Uterine Fibroids

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 982
Author(s):  
Alessandro Zannotti ◽  
Stefania Greco ◽  
Pamela Pellegrino ◽  
Federica Giantomassi ◽  
Giovanni Delli Carpini ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Tissue Repair ◽  
Transforming Growth Factor ◽  
Uterine Fibroids ◽  
Repair Process ◽  
Typical Feature ◽  
Benign Tumors ◽  
Monocyte Chemoattractant Protein 1 ◽  
Gm Csf ◽  
Macrophage Colony

Uterine fibroids represent the most common benign tumors of the uterus. They are considered a typical fibrotic disorder. In fact, the extracellular matrix (ECM) proteins—above all, collagen 1A1, fibronectin and versican—are upregulated in this pathology. The uterine fibroids etiology has not yet been clarified, and this represents an important matter about their resolution. A model has been proposed according to which the formation of an altered ECM could be the result of an excessive wound healing, in turn driven by a dysregulated inflammation process. A lot of molecules act in the complex inflammatory response. Macrophages have a great flexibility since they can assume different phenotypes leading to the tissue repair process. The dysregulation of macrophage proliferation, accumulation and infiltration could lead to an uncontrolled tissue repair and to the consequent pathological fibrosis. In addition, molecules such as monocyte chemoattractant protein-1 (MCP-1), granulocyte macrophage-colony-stimulating factor (GM-CSF), transforming growth factor-beta (TGF-β), activin A and tumor necrosis factor-alfa (TNF-α) were demonstrated to play an important role in the macrophage action within the uncontrolled tissue repair that contributes to the pathological fibrosis that represents a typical feature of the uterine fibroids.

scholarly journals 3D in vitro M2 macrophage model to mimic modulation of tissue repair

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiranuwat Sapudom ◽  
Shaza Karaman ◽  
Walaa K. E. Mohamed ◽  
Anna Garcia-Sabaté ◽  
Brian C. Quartey ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Tissue Repair ◽  
Transforming Growth Factor ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Collagen Matrix ◽  
Repair Process ◽  
M2 Macrophage ◽  
Activated Macrophages

AbstractDistinct anti-inflammatory macrophage (M2) subtypes, namely M2a and M2c, are reported to modulate the tissue repair process tightly and chronologically by modulating fibroblast differentiation state and functions. To establish a well-defined three-dimensional (3D) cell culture model to mimic the tissue repair process, we utilized THP-1 human monocytic cells and a 3D collagen matrix as a biomimetic tissue model. THP-1 cells were differentiated into macrophages, and activated using IL-4/IL-13 (MIL-4/IL-13) and IL-10 (MIL-10). Both activated macrophages were characterized by both their cell surface marker expression and cytokine secretion profile. Our cell characterization suggested that MIL-4/IL-13 and MIL-10 demonstrate M2a- and M2c-like subtypes, respectively. To mimic the initial and resolution phases during the tissue repair, both activated macrophages were co-cultured with fibroblasts and myofibroblasts. We showed that MIL-4/IL-13 were able to promote matrix synthesis and remodeling by induction of myofibroblast differentiation via transforming growth factor beta-1 (TGF-β1). On the contrary, MIL-10 demonstrated the ability to resolve the tissue repair process by dedifferentiation of myofibroblast via IL-10 secretion. Overall, our study demonstrated the importance and the exact roles of M2a and M2c-like macrophage subtypes in coordinating tissue repair in a biomimetic model. The established model can be applied for high-throughput platforms for improving tissue healing and anti-fibrotic drugs testing, as well as other biomedical studies.

scholarly journals Bone marrow and splenic granulocyte-macrophage colony-stimulating factor and transforming growth factor-beta mRNA levels in irradiated mice

Blood ◽  
1995 ◽  
Vol 86 (6) ◽  
pp. 2130-2136 ◽  
Author(s):  
CM Chang ◽  
A Limanni ◽  
WH Baker ◽  
ME Dobson ◽  
JF Kalinich ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Gm Csf ◽  
Protein Levels ◽  
Macrophage Colony Stimulating Factor ◽  
Growth Factor Beta ◽  
Macrophage Colony ◽  
Stimulating Factor

The effects of a myeloablative sublethal 775 cGy 60C gamma radiation exposure on endogenous bone marrow (BM) and splenic granulocyte- macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta (TGF-beta) mRNA levels were assayed in B6D2F1 female mice. BM and spleen were harvested from normal mice and irradiated mice on days 2, 4, 7, 10, and 14 after exposure. Cytokine mRNA levels were determined using reverse transcription-polymerase chain reaction. After irradiation, GM-CSF mRNA levels were significantly increased in the BM from days 2 to 10 and in the spleen from days 4 to 10. However, when BM and splenic GM-CSF protein levels were measured using Western dot blot, no increased protein levels were detected. Serum GM-CSF levels were likewise unchanged. Radiation exposure did not affect BM or splenic TGF- beta mRNA levels and this cytokine is known to be produced by cell populations similar to those that produce GM-CSF. These data suggest that radiation injury to hemopoietic tissues results in differential effects on GM-CSF and TGF-beta mRNA levels and that, in the case of GM- CSF, increased mRNA levels are not matched by increased protein production.

scholarly journals Bidirectional effects of transforming growth factor beta (TGF-beta) on colony-stimulating factor-induced human myelopoiesis in vitro: differential effects of distinct TGF-beta isoforms

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2239-2247 ◽  
Author(s):  
SE Jacobsen ◽  
JR Keller ◽  
FW Ruscetti ◽  
P Kondaiah ◽  
AB Roberts ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hematopoietic Progenitor Cells ◽  
Colony Stimulating Factor ◽  
Tgf Beta ◽  
Hematopoietic Progenitor ◽  
Growth Factor Beta ◽  
Beta 2 ◽  
Macrophage Colony ◽  
Stimulating Factor

Transforming growth factor-beta (TGF-beta) has potent antiproliferative effects on human hematopoietic progenitor cells. We report here that TGF-beta 1 and -beta 2 also exert bimodal dose-dependent stimulation of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte- CSF-induced day 7 granulocyte-macrophage colony-forming units. This increase in colony formation was restricted to low doses (0.01 to 1.0 ng/mL) of TGF-beta 1 and was due to increased granulopoiesis, showing that TGF-beta can affect the differentiation as well as the proliferation of hematopoietic progenitors. Furthermore, TGF-beta 3 was found to be a more potent inhibitor of hematopoietic progenitor cells than TGF-beta 1 and -beta 2. In contrast to the bidirectional proliferative effects of TGF-beta 1 and -beta 2, the effects of TGF- beta 3 on human hematopoiesis were only inhibitory, showing for the first time that TGF-beta isoforms differ not only in potencies but also with regard to the nature of the response they elicit.

scholarly journals Cytokine production by primary bone marrow megakaryocytes

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4151-4156 ◽  
Author(s):  
S Jiang ◽  
JD Levine ◽  
Y Fu ◽  
B Deng ◽  
R London ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Gm Csf

Primary human bone marrow megakaryocytes were studied for their ability to express and release cytokines potentially relevant to their proliferation and/or differentiation. The purity of the bone marrow megakaryocytes was assessed by morphologic and immunocytochemical criteria. Unstimulated marrow megakaryocytes constitutively expressed genes for interleukin-1 beta (IL-1 beta), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), by the polymerase chain reaction (PCR) and Northern blot analysis. At the protein level, megakaryocytes secreted significant amounts of IL-1 beta (53.6 +/- 3.6 pg/mL), IL-6 (57.6 +/- 15.6 pg/mL), and GM-CSF (24 +/- 4 pg/mL) but not TNF-alpha. Exposure of human marrow megakaryocytes to IL-1 beta increased the levels of IL-6 (87.3 +/- 2.3 pg/mL) detected in the culture supernatants. Transforming growth factor- beta was also able to stimulate IL-6, IL-1 beta, and GM-CSF secretion, but was less potent than stimulation with phorbol-12-myristate-13- acetate (PMA). The secreted cytokines acted additively to maintain and increase the number of colony-forming unit-megakaryocytes colonies (approximately 35%). These studies demonstrate the production of multiple cytokines by isolated human bone marrow megakaryocytes constitutively or stimulated in vitro. The capacity of human megakaryocytes to synthesize several cytokines known to modulate hematopoietic cells supports the concept that there may be an autocrine mechanism operative in the regulation of megakaryocytopoiesis.

scholarly journals Transforming growth factor beta abrogates the effects of hematopoietins on eosinophils and induces their apoptosis.

1994 ◽  
Vol 179 (3) ◽  
pp. 1041-1045 ◽  
Author(s):  
R Alam ◽  
P Forsythe ◽  
S Stafford ◽  
Y Fukuda
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Dependent Manner ◽  
Tgf Beta ◽  
Gm Csf ◽  
Eosinophil Survival ◽  
Growth Factor Beta ◽  
Induced Apoptosis ◽  
And Function

Hematopoietins, interleukin (IL)-3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) have previously been shown to prolong eosinophil survival and abrogate apoptosis. The objective of this study was to investigate the effect of transforming growth factor beta (TGF-beta) on eosinophil survival and apoptosis. Eosinophils from peripheral blood of mildly eosinophilic donors were isolated to > 97% purity using discontinuous Percoll density gradient. Eosinophils were cultured with hematopoietins with or without TGF-beta for 4 d and their viability was assessed. We confirmed previous observations that hematopoietins prolonged eosinophil survival and inhibited apoptosis. TGF-beta at concentrations > or = 10(-12) M abrogated the survival-prolonging effects of hematopoietins in a dose-dependent manner and induced apoptosis as determined by DNA fragmentation in agarose gels. The effect of TGF-beta was blocked by an anti-TGF-beta antibody. The anti-TGF-beta antibody also prolonged eosinophil survival on its own. The culture of eosinophils with IL-3 and GM-CSF stimulated the synthesis of GM-CSF and IL-5, respectively, suggesting an autocrine mechanism of growth factor production. TGF-beta inhibited the synthesis of GM-CSF and IL-5 by eosinophils. TGF-beta did not have any effect on the expression of GM-CSF receptors on eosinophils. We also studied the effect of TGF-beta on eosinophil function and found that TGF-beta inhibited the release of eosinophil peroxidase. Thus, TGF-beta seems to inhibit eosinophil survival and function. The inhibition of endogenous synthesis of hematopoietins may be one mechanism by which TGF-beta blocks eosinophil survival and induces apoptosis.

scholarly journals Comparison of the Inflammatory Responses of Human Meningeal Cells following Challenge with Neisseria lactamica and with Neisseria meningitidis

2006 ◽  
Vol 74 (11) ◽  
pp. 6467-6478 ◽  
Author(s):  
Mark I. Fowler ◽  
Kiave Y. Ho Wang Yin ◽  
Holly E. Humphries ◽  
John E. Heckels ◽  
Myron Christodoulides
Keyword(s):  
Neisseria Meningitidis ◽  
Inflammatory Responses ◽  
Host Cells ◽  
Pathogenic Potential ◽  
Monocyte Chemoattractant Protein 1 ◽  
Gm Csf ◽  
Neisseria Lactamica ◽  
Meningeal Cells ◽  
Macrophage Colony

ABSTRACT The rationale for the present study was to determine how different species of bacteria interact with cells of the human meninges in order to gain information that would have broad relevance to understanding aspects of the innate immune response in the brain. Neisseria lactamica is an occasional cause of meningitis in humans, and in this study we investigated the in vitro interactions between N. lactamica and cells derived from the leptomeninges in comparison with the closely related organism Neisseria meningitidis, a major cause of meningitis worldwide. N. lactamica adhered specifically to meningioma cells, but the levels of adherence were generally lower than those with N. meningitidis. Meningioma cells challenged with N. lactamica and N. meningitidis secreted significant amounts of the proinflammatory cytokine interleukin-6 (IL-6), the C-X-C chemokine IL-8, and the C-C chemokines monocyte chemoattractant protein 1 (MCP-1) and RANTES, but it secreted very low levels of the cytokine growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). Thus, meningeal cells are involved in the innate host response to Neisseria species that are capable of entering the cerebrospinal fluid. The levels of IL-8 and MCP-1 secretion induced by both bacteria were essentially similar. By contrast, N. lactamica induced significantly lower levels of IL-6 than N. meningitidis. Challenge with the highest concentration of N. lactamica (108 CFU) induced a small but significant down-regulation of RANTES secretion, which was not observed with lower concentrations of bacteria. N. meningitidis (106 to 108 CFU) also down-regulated RANTES secretion, but this effect was significantly greater than that observed with N. lactamica. Although both bacteria were unable to invade meningeal cells directly, host cells remained viable on prolonged challenge with N. lactamica, whereas N. meningitidis induced death; the mechanism was overwhelming necrosis with no significant apoptosis. It is likely that differential expression of modulins between N. lactamica and N. meningitidis contributes to these observed differences in pathogenic potential.

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