Table 1.
Summary of effects produced by prostglandin E2 (PGE2) in isolated cells of the respiratory tract, in animal models of airway disease, and in humans with airway disease
| Response to PGE2 | EP receptor (species if not human) | Reference | |
|---|---|---|---|
| In vitro effects of PGE2 on | |||
| Airway smooth muscle | Relaxation | EP2 | Norel et al. (1999) |
| ↓Proliferation | EP2 | Burgess et al. (2004); Kassel et al. (2008) | |
| ↓Migration | ? | Goncharova et al. (2003) | |
| ↓RANTES, ICAM, GM-CSF, Il-8, eotaxin, MCP-1 | ? | Ammit et al. (2000); Lazzeri et al. (2001); Wuyts et al. (2003); Kaur et al. (2008) | |
| ↑VEGF, G-CSF, Il-6 | EP2/EP4 | Ammit et al. (2000); Bradbury et al. (2005); Clarke et al. (2005) | |
| Epithelial | ↑Cilia beat frequency | ? | Bonin et al. (1992); Schuil et al. (1995); Haxel et al. (2001) |
| ↑Cl-channel conductance | EP4 (frog, cow) | Clayton et al. (2005); Palmer et al. (2006); Joy and Cowley (2008); Seto et al. (2008) | |
| ↑Na+ transport | EP1/EP2 (frog) | Berk et al. (2004) | |
| ↑Mucin secretion | EP4 | Kook Kim et al. (2006) | |
| ↑MUC5A/8 expression | EP4 | Cho et al. (2005); Kook Kim et al. (2006); Song et al. (2009) | |
| ↑Rate of wound closure | EP1/EP4/EP2? | Savla et al. (2001) | |
| ↓Il-8 & ET-1 secretion | EP3/EP4 | Pelletier et al. (2001); Hattori et al. (2008) | |
| ↑Il-6 release | EP2/EP4 | Tavakoli et al. (2001) | |
| Submucosal gland | ↑Ionic currents & secretory function | ? (pig) | Liu et al. (2005) |
| ↑Sensitivity to acetylcholine | EP2 (pig) | Liu and Farley (2007) | |
| Cholinergic nerve | ↓Acetylcholine release | EP3 (guinea pig, dog) | Deckers et al. (1989); Zhao et al. (1994); Spicuzza et al. (1998); Clarke et al. (2004) |
| Sensory nerve (pulmonary C-fibre afferents) | ↑Sensitivity to chemical stimulants | EP2 (rat) | Ho et al. (2000); Kwong and Lee (2002; 2005;) |
| Alveolar type II | ↑Surfactant secretion | EP1 (rat) | Marino and Rooney (1980); Morsy et al. (2001) |
| ↑Na+ uptake | EP3 | Mukhopadhyay et al. (1998) | |
| Pulmonary endothelial | ↑Barrier function | Birukova et al. (2007) | |
| Alveolar macrophage | ↓Phagocytosis | EP2 (mouse/rat) | Canning et al. (1991); Aronoff et al. (2004); Canetti et al. (2007); Brock et al. (2008); Lee et al. (2009); Medeiros et al. (2009) |
| ↓Bacterial killing | EP2/EP4 | Serezani et al. (2007) | |
| ↓Mitochondrial inner membrane perturbation and necrosis | EP2 | Chen et al. (2008) | |
| ↓TNF-α | EP2/EP4 | Ratcliffe et al. (2007) | |
| ↑Il-10 & NO release | ? (rat) | Menard et al. (2007) | |
| Fibroblast | ↓proliferation | EP2 | Bitterman et al. (1986); Liu et al. (2004); Huang et al. (2007); Huang et al. (2008) |
| ↓Collagen production | EP2 | Saltzman et al. (1982); Fine et al. (1989); Liu et al. (2004); Huang et al. (2007); Huang et al. (2008) | |
| ↓Fibroblast to myofibroblast transition | ? | Kolodsick et al. (2003) | |
| ↓Myofibroblast differentiation | Dunkern et al. (2007) | ||
| ↓Migration | EP2 | Kohyama et al. (2001); White et al. (2005) | |
| ↓Smoke-induced apoptosis | EP2 | Sugiura et al. (2007) | |
| Mast cell | ↓Migration | EP3? | Duffy et al. (2008) |
| ↓Histamine release | EP2 | Drury et al. (1998); Kay et al. (2006); Duffy et al. (2008) | |
| Dendritic cell | ↑Podosome dissolution | van Helden et al. (2008) | |
| ↑Migration | EP2/EP4 | Legler et al. (2006) | |
| ↑Maturation | EP2/EP4 | Kubo et al. (2004) | |
| ↓CCL3 and CCL4 | EP2/EP4 (mouse) | Jing et al. (2003) | |
| ↑Resistance to apoptosis | EP2/EP4 | Baratelli et al. (2005a) | |
| ↓TNF-α release & antigen presentation | ? (mouse) | Kambayashi et al. (2001) | |
| T cells | ↓Proliferation | ? | Jarvinen et al. (2008) |
| ↑Il-10 expression | ? | Benbernou et al. (1997) | |
| Treg | ↑Inhibitory function & differentiation | ? | Baratelli et al. (2005b) |
| ↑Expansion | ? | Garg et al. (2008) | |
| Eosinophils | ↓Migration | EP2/EP4 | Sturm et al. (2008) |
| ↓Release from bone marrow | ? (guinea pig) | Sturm et al. (2008) | |
| ↓Degranulation | EP2/EP4 | Sturm et al. (2008) | |
| ↓PAF-induced aggregation | EP2 (guinea pig) | Teixeira et al. (1997) | |
| Neutrophils | ↓Chemotaxis | EP2? | Armstrong (1995) |
| B cells | ↓Proliferation | EP4 (mouse) | Murn et al. (2008) |
| Promotes differentiation and Il-4 and LPS-driven class switching to IgE | EP2/EP4 (mouse) | Fedyk and Phipps (1996) | |
| In vivo effects of PGE2 in | |||
| Normal animals or subjects | Bronchodilatation | EP2 (mouse) | Mathe and Hedqvist (1975); Smith et al. (1975); Sheller et al. (2000); Tilley et al. (2003) |
| Asthmatics (allergic) | Bronchodilatation | Smith et al. (1975) | |
| ↓Early and late response to allergen | Pavord et al. (1993); Gauvreau et al. (1999) | ||
| ↓Airway hyperresponsiveness and sputum eosinophils | Gauvreau et al. (1999) | ||
| ↓BAL PGD2, ↓BAL eosinophils | Hartert et al. (2000) | ||
| Asthmatic (exercise) | ↓Exercise-induced bronchoconstriction | Melillo et al. (1994) | |
| Allergic inflammation | ↓Allergen-induced bronchoconstriction | EP2/EP4 (guinea pig) | Martin et al. (2002); Tanaka et al. (2005) |
| ↓BAL eosinophils | ? (mouse, rat) | Martin et al. (2002); De Campo and Henry (2005); Sturm et al. (2008) | |
| ↓BAL LTs, ↓T cell cytokine expression | ? (rat) | Martin et al. (2002) | |
| Bleomycin-induced fibrosis | PGE2 synthetic analogue 16,16-dimethyl-PGE2↓infiltration by leukocytes, ↓myeloperoxidase activity, ↓Il-1, TNF-α and nitrotyrosine, ↓lung edema & injury, ↓collagen deposition, ↓weight loss and mortality | ? (mouse) | Failla et al. (2009) |
Not all references to PGE2-induced responses are cited, with preference given to studies that have used human cells, tissues or subjects. Animal studies are cited where human studies have not been reported, or to indicate which E-prostanoid (EP) receptor subtype mediated the response.