. Author manuscript; available in PMC: 2019 Nov 1.

Published in final edited form as: Pharmacol Res. 2018 Oct 28;137:252–258. doi: 10.1016/j.phrs.2018.10.026

Table 1.

Criteria for classification as a resolution promoting factor (RPF) and comparison of matrix metalloproteinase (MMP)-12 to known RPFs

	MMP-12	Resolvins	Annexin A1
Increases after MI	Yes⁽⁸⁾	Yes⁽⁹¹⁾	Yes⁽⁹²⁾
Regulates leukocyte trafficking	Yes	Yes	Yes
Regulates leukocyte trafficking	↑ monocyte/ neutrophil chemotaxis after injury^{(42, 44)}	↓ neutrophil transendothelial migration⁽⁹³⁾ ↓ neutrophil chemotaxis from spleen⁽¹⁵⁾	↓ CD68+ macrophages after MI⁽⁹²⁾ ↓ neutrophil transendothelial migration⁽⁹⁴⁾
Reduces proinflammation	Yes	Yes	Yes
Reduces proinflammation	↓ IL1rl, IL6ra, IL11, and Cxcr5 after MI⁽⁸⁾ ↓ IFN-α, CCL2, complement proteins, NETS, OPN, CD 14 ^{(46, 48, 49, 51, 52)}	↓ cytokine and chemokines⁽⁹⁵⁾ ↓ NF-κB, STAT3, MAPK activity⁽⁹⁵⁾	↓ pro-inflammatory and pro-thrombotic cytokines⁽⁹⁴⁾
Increases antiinflammation	Yes	Yes	Yes
Increases antiinflammation	↑ IL-13 activity^{(55, 56)} ↑ TGF-β1 activity⁽²⁵⁾ ↑ IL-8 secretion⁽⁹⁶⁾ ↑ Th2 cell activity⁽⁵⁸⁾ ↑ globular adiponectin⁽⁶⁰⁾	↑ SIRT1 expression⁽⁹⁵⁾ ↑ M2 markers—Mrc1, Arg1, Ym1⁽¹⁵⁾	↑ IL-10 expression⁽⁹²⁾ ↑ TGF-β secretion⁽⁹⁷⁾ Activation of lipoxin A4 receptor⁽⁹⁸⁾
Promotes cell clearance	Yes	Yes	Yes
Promotes cell clearance	↑ neutrophil clearance from arthritic joints⁽⁴⁸⁾ ↑ neutrophil apoptosis after MI⁽⁸⁾ ↑ macrophage phagocytosis⁽⁶⁵⁾	↑ neutrophil efflux after MI(99) ↑ neutrophil apoptosis⁽¹⁰⁰⁾	↑ macrophage phagocytosis of apoptotic neutrophils⁽¹⁰¹⁾
Promotes scar formation and angiogenesis	Yes	No	Yes
Promotes scar formation and angiogenesis	↑ degradation of myocyte debris⁽⁷³⁾ ↑ ECM turnover and remodeling^{(8, 25)} ↓ tissue degradation by other MMPs^{(8, 55)} ↑ TGF-β1 activity in myofibroblasts⁽⁸⁰⁾ ↑ fibroblast proliferation⁽⁸²⁾	↓ fibrosis/collagen accumulation after MI⁽¹⁵⁾	↑ fibroblast activation and collagen deposition⁽¹⁰²⁾

Arg 1- arginase 1; CCL- CC chemokine ligand; CD- cluster of differentiation; CXCR- CXC chemokine receptor; ECM- extracellular matrix; IFN- interferon; IL-interleukin; MAPK- mitogen activated protein kinase; MRC1- mannose receptor C type 1; NET- neutrophil extracellular trap; NF-κB- nuclear factor kB; OPN- osteopontin; Stat- signal transducer and activator of transcription; TGF- transforming growth factor; Ym1- chitinase-like protein 3