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Juxtacrine interaction of macrophages and bone marrow stromal cells induce interleukin-6 signals and promote cell migration.

Chang J, Koh AJ, Roca H, McCauley LK - Bone Res (2015)

Bottom Line: In the current study, we investigated the in vitro interaction of murine macrophages and bone marrow stromal cells (BMSCs), with focus on the juxtacrine induction of IL-6 signaling and the resultant effect on BMSC migration and growth.Meanwhile, macrophage derived IL-6 remained important for the overall production of IL-6 protein in the co-cultures.Taken together, these findings show the function of macrophages as co-inducers of migration and growth of BMSCs, which could directly influence bone formation and turnover.

View Article: PubMed Central - PubMed

Affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry , Ann Arbor, MI 48109, USA ; Department of Periodontology, University of Florida College of Dentistry , Gainesville, FL 32610, USA.

ABSTRACT
The bone marrow contains a heterogeneous milieu of cells, including macrophages, which are key cellular mediators for resolving infection and inflammation. Macrophages are most well known for their ability to phagocytose foreign bodies or apoptotic cells to maintain homeostasis; however, little is known about their function in the bone microenvironment. In the current study, we investigated the in vitro interaction of murine macrophages and bone marrow stromal cells (BMSCs), with focus on the juxtacrine induction of IL-6 signaling and the resultant effect on BMSC migration and growth. The juxtacrine interaction of primary mouse macrophages and BMSCs activated IL-6 signaling in the co-cultures, which subsequently enhanced BMSC migration and increased BMSC numbers. BMSCs and macrophages harvested from IL-6 knockout mice revealed that IL-6 signaling was essential for enhancement of BMSC migration and increased BMSC numbers via juxtacrine interactions. BMSCs were the main contributor of IL-6 signaling, and hence activation of the IL-6/gp130/STAT3 pathway. Meanwhile, macrophage derived IL-6 remained important for the overall production of IL-6 protein in the co-cultures. Taken together, these findings show the function of macrophages as co-inducers of migration and growth of BMSCs, which could directly influence bone formation and turnover.

No MeSH data available.


Related in: MedlinePlus

BMSCs were the main contributing cells for IL-6 protein production from juxtacrine interaction. ELISA assay showed that after 24 hours, IL-6 protein was significantly increased in the supernatant from co-culture of WT BMSCs and WT macrophages, and co-culture of WT BMSCs and IL-6 KO macrophages. No elevation of IL-6 protein concentration was found in the co-cultures of IL-6 KO BMSCs and either WT macrophages or IL-6 KO macrophages. Data are mean ± SEM (n = 2 in each group); **P < 0.01.
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fig4: BMSCs were the main contributing cells for IL-6 protein production from juxtacrine interaction. ELISA assay showed that after 24 hours, IL-6 protein was significantly increased in the supernatant from co-culture of WT BMSCs and WT macrophages, and co-culture of WT BMSCs and IL-6 KO macrophages. No elevation of IL-6 protein concentration was found in the co-cultures of IL-6 KO BMSCs and either WT macrophages or IL-6 KO macrophages. Data are mean ± SEM (n = 2 in each group); **P < 0.01.

Mentions: A previous report suggested that human BMSCs were the primary cells to produce IL-6 protein when co-cultured with human myeloid cancer cells.11 However, the direct evidence for this speculation was not provided. In order to clarify whether it was BMSCs, macrophages, or both, which generate IL-6, co-cultures were established with WT-BMSCs and WT-macrophages, WT-BMSCs and IL-6 KO-macrophages, IL-6 KO-BMSCs and WT-macrophages, IL-6 KO-BMSCs and IL-6 KO-macrophages. The analysis of conditioned medium from these four groups and their single culture controls resulted in ∼50% reduction of IL-6 protein in WT-BMSC + IL-6 KO-macrophage cultures compared with co-cultures from WT cells. IL-6 KO in BMSCs demonstrated low levels of IL-6 protein in the conditioned media, regardless of the phenotype of macrophages (Figure 4).


Juxtacrine interaction of macrophages and bone marrow stromal cells induce interleukin-6 signals and promote cell migration.

Chang J, Koh AJ, Roca H, McCauley LK - Bone Res (2015)

BMSCs were the main contributing cells for IL-6 protein production from juxtacrine interaction. ELISA assay showed that after 24 hours, IL-6 protein was significantly increased in the supernatant from co-culture of WT BMSCs and WT macrophages, and co-culture of WT BMSCs and IL-6 KO macrophages. No elevation of IL-6 protein concentration was found in the co-cultures of IL-6 KO BMSCs and either WT macrophages or IL-6 KO macrophages. Data are mean ± SEM (n = 2 in each group); **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4637844&req=5

fig4: BMSCs were the main contributing cells for IL-6 protein production from juxtacrine interaction. ELISA assay showed that after 24 hours, IL-6 protein was significantly increased in the supernatant from co-culture of WT BMSCs and WT macrophages, and co-culture of WT BMSCs and IL-6 KO macrophages. No elevation of IL-6 protein concentration was found in the co-cultures of IL-6 KO BMSCs and either WT macrophages or IL-6 KO macrophages. Data are mean ± SEM (n = 2 in each group); **P < 0.01.
Mentions: A previous report suggested that human BMSCs were the primary cells to produce IL-6 protein when co-cultured with human myeloid cancer cells.11 However, the direct evidence for this speculation was not provided. In order to clarify whether it was BMSCs, macrophages, or both, which generate IL-6, co-cultures were established with WT-BMSCs and WT-macrophages, WT-BMSCs and IL-6 KO-macrophages, IL-6 KO-BMSCs and WT-macrophages, IL-6 KO-BMSCs and IL-6 KO-macrophages. The analysis of conditioned medium from these four groups and their single culture controls resulted in ∼50% reduction of IL-6 protein in WT-BMSC + IL-6 KO-macrophage cultures compared with co-cultures from WT cells. IL-6 KO in BMSCs demonstrated low levels of IL-6 protein in the conditioned media, regardless of the phenotype of macrophages (Figure 4).

Bottom Line: In the current study, we investigated the in vitro interaction of murine macrophages and bone marrow stromal cells (BMSCs), with focus on the juxtacrine induction of IL-6 signaling and the resultant effect on BMSC migration and growth.Meanwhile, macrophage derived IL-6 remained important for the overall production of IL-6 protein in the co-cultures.Taken together, these findings show the function of macrophages as co-inducers of migration and growth of BMSCs, which could directly influence bone formation and turnover.

View Article: PubMed Central - PubMed

Affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry , Ann Arbor, MI 48109, USA ; Department of Periodontology, University of Florida College of Dentistry , Gainesville, FL 32610, USA.

ABSTRACT
The bone marrow contains a heterogeneous milieu of cells, including macrophages, which are key cellular mediators for resolving infection and inflammation. Macrophages are most well known for their ability to phagocytose foreign bodies or apoptotic cells to maintain homeostasis; however, little is known about their function in the bone microenvironment. In the current study, we investigated the in vitro interaction of murine macrophages and bone marrow stromal cells (BMSCs), with focus on the juxtacrine induction of IL-6 signaling and the resultant effect on BMSC migration and growth. The juxtacrine interaction of primary mouse macrophages and BMSCs activated IL-6 signaling in the co-cultures, which subsequently enhanced BMSC migration and increased BMSC numbers. BMSCs and macrophages harvested from IL-6 knockout mice revealed that IL-6 signaling was essential for enhancement of BMSC migration and increased BMSC numbers via juxtacrine interactions. BMSCs were the main contributor of IL-6 signaling, and hence activation of the IL-6/gp130/STAT3 pathway. Meanwhile, macrophage derived IL-6 remained important for the overall production of IL-6 protein in the co-cultures. Taken together, these findings show the function of macrophages as co-inducers of migration and growth of BMSCs, which could directly influence bone formation and turnover.

No MeSH data available.


Related in: MedlinePlus