Relaxin promotes clustering, migration, and activation states of mononuclear myelocytic cells.
Monocytes are leukocytic precursors of macrophages, dendritic cells, and osteoclasts, with critical roles in inflammation and tumor biology. Tumors can elicit signals that activate monocytes to extravasate, infiltrate tumors, and differentiate into tumor-associated macrophages (TAMs), which can modulate host immune surveillance. In order to assess whether relaxin can influence monocyte activation status, we assessed its ability to alter cell-cell clustering and cytokine expression of the monocytic cell line THP-1. Here we report that relaxin can induce time- and substrate-dependent homotypic cell-cell clustering of monocytes. In addition, we demonstrate that relaxin can suppress macrophage migration in an adenylate cyclase-independent, nitric oxide synthase-dependent fashion. We confirm relaxin-induced upregulation of vascular endothelial growth factor expression and regulation of M1/M2 cytokine profiles. By stimulating monocyte activation and modulating inflammatory cytokine expression and migratory activity of resulting macrophages in response to endotoxin exposure, relaxin may be a critical regulator of the macrophage activation state that regulates the TAM phenotype.
The Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia, Canada.
Kevin A
KA
Figueiredo
Gina
G
Rossi
Michael E
ME
Cox
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012065:Relaxin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D012065:Relaxin