title: Attenuation of the programmed cell death-1 pathway increases the M1 polarization of macrophages induced by zymosan.
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.
authors.affiliation: Department of Medical Science of Laboratory, Liaoning University of Traditional Chinese Medicine, Shenyang, China.|Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, China.|Graduate Institute, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
authors.forename: L
authors.initials: L
authors.lastname: Jia
authors.affiliation: College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Medical College, University of South China, Hengyang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D017209:Apoptosis; D060890:B7-H1 Antigen / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000209:etiology; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000172:deficiency / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D060890:B7-H1 Antigen; C491768:Ccl2 protein, mouse; C498919:Cd274 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; C494080:Stat1 protein, mouse; C494100:Stat6 protein, mouse; D051996:Transcription Factor RelA; D015054:Zymosan; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse