TIM-1 regulates macrophage cytokine production and B7 family member expression.
T-cell immunoglobulin mucin-1 (TIM-1) is associated with the regulation of T helper type 2 (Th2) immune responses and has been associated with asthma susceptibility. Previous studies have shown that administration of TIM-1 results in T cell hyperproliferation and increased Th2 cytokine secretion. TIM-1 has also been shown to bind to macrophages, but the effects of TIM-1 administration on macrophage activity have not been assessed. In this study we demonstrate that TIM-1 binds to the mouse macrophage cell line RAW 264.7. Stimulation of the RAW264.7 cells with TIM-1 increases nitric oxide production. A dramatic increase in the pro-inflammatory cytokines TNF-alpha and IL-6 is seen upon TIM-1 stimulation of RAW 264.7 cells. Additionally, there is a moderate increase in the immuno-modulatory cytokine IL-10 when RAW 264.7 cells are stimulated with TIM-1. TIM-1 stimulation also alters the expression of some members of the B7 family of co-stimulatory/co-inhibitory proteins. TIM-1 stimulation leads to increased B7-1, B7-H1, and PD-L2 expression, while inhibiting B7-H2 expression. These studies suggest that TIM-1 can regulate macrophage activation and alter the co-stimulatory properties of macrophages and thus may contribute to allergic inflammatory diseases such as asthma.
Hein
Renee M
RM
Bioassay Department, R&D Systems, Inc., 614 McKinley Place N.E., Minneapolis, MN 55413, USA.
Woods
Melody L
ML
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism; D002460:Cell Line; D000072596:Hepatitis A Virus Cellular Receptor 1; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011991:Receptors, Virus / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide