Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways.
Monocytes/macrophages are heterogeneous and versatile cells that could undergo their phenotypically/functionally dynamic switch in response to the microenvironment signals. Two major macrophage subpopulations with different functions which represent extreme of a continuum in a universe of activation states, including classically activated/inflammatory (M1) and alternatively activated/regenerative (M2) macrophages, have long been recognized. Emerging evidence through genetic or pharmacologic approaches has now been made in defining the actual fate in vivo and in vitro underlying M1 or M2-like polarized activation under physiological and pathological conditions. These cells are characterized by their expression of cell surface markers, secreted cytokines and chemokines, and transcription and epigenetic pathways. Here in this review, we shed new light on the contribution of several major signaling pathways and their modulators/targets involved in directing the macrophage plasticity and polarized function, assess the mechanisms of macrophage polarization by interacting endogenous cellular mechanisms and molecules associated with reciprocal skewing of macrophage polarization between the M1 and M2 states. The identification of mechanisms underlying functional polarization of macrophages into M1 or M2 cells might provide new insights into a basis for macrophage-centered diagnostic and therapeutic strategies for multiple diseases.
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China.
Dexi
D
Zhou
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China.
Cheng
C
Huang
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China.
Zhen
Z
Lin
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China.
Shuxiang
S
Zhan
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China.
Lingna
L
Kong
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Department of Ophthalmology, The 1st Affiliated Hospital of Anhui Medical University, Hefei, China.
Chengbo
C
Fang
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
Jun
J
Li
D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction
D051880:Receptors, Notch; D050791:STAT Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases
ACE; AMP-activated protein kinase; AMPK; AP-1; AT1; ATMs; Adipose tissue macrophages; Arg-1; BMDM; C-Jun N-terminal kinases; C/EBP; CAAT/enhancer-binding proteins; CCR2; CM; Cellular signaling pathway; C–C motif chemokine receptor 2; GM-CSF; HFD; HMDM; IRF; JNKs; KCs; LPS; M-CSF; MAPKs; MLK3; Macrophage polarization; MicroRNAs; NAFLD; NICD; Notch intracellular domain; PBMC; PI3K; PPAR; Phenotypic switch; SLE; SOCS; STAT; TAMs; TLR; Toll-like receptor; activator protein-1; angiotensin type 1; angiotensin-converting enzyme; arginine-1; bone marrow-derived macrophages; conditioned medium; granulocyte-macrophage colony-stimulating factor; high-fat diet; human monocyte-differentiated macrophage; iNOS; inducible nitric oxide synthase; interferon regulatory factor; kupffer cells; lipopolysaccharide; macrophage CSF; miR; microRNA; mitogen-activated protein kinases; mixed-lineage kinase 3; nonalcoholic fatty liver disease; peripheral blood monocytes; peroxisome proliferator-activated receptor; phosphatidylinositol-3-kinase; signal transducers and activators of transcription; suppressor of cytokine signaling; systemic lupus erythematosus; tumor-associated macrophages