Fibroblasts regulate monocyte response to ECM-derived matrix: the effects on monocyte adhesion and the production of inflammatory, matrix remodeling, and growth factor proteins.
Monocytes/macrophages and fibroblasts are recruited to the injury site and orchestrate the host response and tissue repair. We have previously shown that polyethylene glycol (PEG)-ylated arginine-glycine-aspartic acid (RGD) sequence grafted onto an extracellular matrix (ECM)-based semi-interpenetrating network (sIPN) enhances monocyte adhesion, and modulates subsequent gene expression and release of inflammatory and matrix remodeling factors. In this study, we investigate the direct influence of fibroblasts on monocyte response to this ECM mimic. Key wound-healing factors in inflammation, matrix remodeling, and regeneration were analyzed to gain insight into the interrelated role of regulation in fibroblast-monocyte interaction. Interleukin-1alpha/-1beta (IL-1alpha/-1beta), interleukin-6 (IL-6), tumor necrosis factor- alpha (TNF-alpha), monocyte inflammatory protein-1alpha/-1beta (MIP-1alpha/-1beta), transforming growth factor-alpha (TGF-alpha), monocyte chemoattractant factor (MCP-1), matrix metalloproteinase-2/-9 (MMP-2/-9), vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed. Fibroblasts decreased monocyte adhesion onto the RGD-grafted sIPN while increasing monocyte GM-CSF on all surfaces over time except for on RGD and PHSRN-grafted sIPN at 96 h. Monocytes decreased initial fibroblast IL-1alpha and TGF-alpha, but drastically increased fibroblast MMP-2 and GM-CSF. Monocyte IL-1beta, TNF-alpha, MIP-1beta, MCP-1, MMP-9, and GM-CSF expression was increased over time in the presence of all sIPNs, and when the sIPNs were immobilized with ligands, a down-regulation of fibroblast IL-1beta, MIP-1alpha, MIP-1beta compared with unmodified sIPN was observed. When the ligand immobilized was RGD, monocyte TGF-alpha, MIP-1beta, and VEGF expression was increased while monocyte GM-CSF was decreased at selected time points. These results showed a dynamic monocyte response to selected ECM components in the presence of fibroblasts.
Chung
Amy S
AS
School of Pharmacy, Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Wisconsin, USA.
Kao
Weiyuan John
WJ
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D054407:Chemokine CCL4 / Q000378:metabolism; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008024:Ligands; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009842:Oligopeptides / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D054407:Chemokine CCL4; D036341:Intercellular Signaling Peptides and Proteins; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D008024:Ligands; D009842:Oligopeptides; D016211:Transforming Growth Factor alpha; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9