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Engineering macrophages to control the inflammatory response and angiogenesis.

ABSTRACT: Macrophage (M?) dysregulation is increasingly becoming recognized as a risk factor for a number of inflammatory complications including atherosclerosis, cancer, and the host response elicited by biomedical devices. It is still unclear what roles the pro-inflammatory (M1) M? and pro-healing (M2) M? phenotypes play during the healing process. However, it has been shown that a local overabundance of M1 M?s can potentially lead to a chronically inflamed state of the tissue; while a local over-exuberant M2 M? response can lead to tissue fibrosis and even promote tumorigenesis. These notions strengthen the argument that the tight temporal regulation of this phenotype balance is necessary to promote inflammatory resolution that leads to tissue homeostasis. In this study, we have engineered pro-inflammatory M?s, M?-cTLR4 cells, which can be activated to a M1-like M? phenotype with a small molecule, the chemical inducer of dimerization (CID) drug. The M?-cTLR4 cells when activated with the CID drug, express increased levels of TNF?, IL-6, and iNOS. Activated M?-cTLR4 cells stay stimulated for at least 48h; once the CID drug is withdrawn, the M?-cTLR4 cells return to baseline state within 18h. Further, in vitro CID-activated M?-cTLR4 cells induce upregulation of VCAM-1 and ICAM-1 on endothelial cells (EC) in a TNF?-dependent manner. With the ability to specifically modulate the M?-cTLR4 cells with the presence or absence of a small molecule, we now have the tool necessary to observe a primarily M1 M? response during inflammation. By isolating this phase of the wound healing response, it may be possible to determine conditions for ideal healing.

SUBMITTER: Eaton KV

PROVIDER: S-EPMC4679554 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Engineering macrophages to control the inflammatory response and angiogenesis.

Eaton K V KV Yang H L HL Giachelli C M CM Scatena M M

Experimental cell research 20151121 2

Macrophage (MΦ) dysregulation is increasingly becoming recognized as a risk factor for a number of inflammatory complications including atherosclerosis, cancer, and the host response elicited by biomedical devices. It is still unclear what roles the pro-inflammatory (M1) MΦ and pro-healing (M2) MΦ phenotypes play during the healing process. However, it has been shown that a local overabundance of M1 MΦs can potentially lead to a chronically inflamed state of the tissue; while a local over-exuber ...[more]

PMID: 26610863

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Engineering macrophages to control the inflammatory response and angiogenesis.

Publications

Engineering macrophages to control the inflammatory response and angiogenesis.

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