Abstract
Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals on interaction with its 2 ligands, PD-L1 and PD-L2. We assessed the contribution of the PD-1 pathway to regulating the polarization of macrophages that promote inflammation induced by zymosan. We found that PD-1(-/-) mice developed robust peritonitis with more abundant infiltration of M1 macrophages, accompanied by higher levels of pro-inflammation factors, especially monocyte chemotactic protein-1 (MCP-1) compared with wild-type controls ex vivo and in vitro. Our results indicated that PD-1 deficiency promotes M1 rather than M2 polarization of macrophages by enhancing the expression of p-STAT1/p-NF-κB p65 and downregulating p-STAT6. We found that PD-1 engagement followed by zymosan stimulation might primarily attenuate the phosphorylation of tyrosine residue in PD-1 receptor/ligand and the recruitment of SHP-2 to PD-1 receptor/ligand, leading to the reduction of M1 type cytokine production.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis
-
B7-H1 Antigen / metabolism
-
Cell Polarity / drug effects
-
Chemokine CCL2 / genetics
-
Chemokine CCL2 / metabolism
-
Cytokines / analysis
-
Cytokines / genetics
-
Cytokines / metabolism
-
Macrophages / cytology
-
Macrophages / drug effects*
-
Macrophages / metabolism
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Peritonitis / etiology
-
Programmed Cell Death 1 Ligand 2 Protein / metabolism
-
Programmed Cell Death 1 Receptor / deficiency
-
Programmed Cell Death 1 Receptor / genetics*
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
-
STAT1 Transcription Factor / metabolism
-
STAT6 Transcription Factor / metabolism
-
Signal Transduction / drug effects
-
Transcription Factor RelA / metabolism
-
Zymosan / pharmacology*
Substances
-
B7-H1 Antigen
-
Ccl2 protein, mouse
-
Cd274 protein, mouse
-
Chemokine CCL2
-
Cytokines
-
Pdcd1 protein, mouse
-
Pdcd1lg2 protein, mouse
-
Programmed Cell Death 1 Ligand 2 Protein
-
Programmed Cell Death 1 Receptor
-
STAT1 Transcription Factor
-
STAT6 Transcription Factor
-
Stat1 protein, mouse
-
Stat6 protein, mouse
-
Transcription Factor RelA
-
Zymosan
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11
-
Ptpn11 protein, mouse