Table 1.

Sphingosine 1-phosphate (S1P) signaling in lung disorders: the effects of different inhibitors of SphKs, S1P receptor modulators, and S1P antibody in different diseases related to lung with possible mechanism of action.

S. no.	Drug used	Disease	Model	Mechanism of action	Reference
1	JTE-013	Asthma	Human bronchial smooth muscle (BSM) cells	Suppression of S1P-induced inhibition of RANTES production	(18)
2	JTE-013	Asthma	Mouse model of allergic airway inflammation	Inhibition of S1P-mediated BSM contraction	(19)
3	SKI-II	Asthma	Ovalbumin-sensitized mouse model	Alleviation of BSM hyperresponsiveness	(20)
4	Inhibitor of SphK1	Asthma	Mast cell-dependent mouse model of ovalbumin-induced asthma	Inhibition of antigen-dependent mast cell activation and NF-κB activation	(21)
5	FTY720	Asthma	Antigen-sensitized murine asthma model	Inhibition of Th1- and Th2-mediated airway inflammation, inhibition of T cell, and eosinophil infiltration into bronchial tissue	(23)
6	FTY720, S1P	Asthma	Mouse asthma model	Suppression of Th2-dependent eosinophilic airway inflammation and bronchial hyperresponsiveness	(24)
7	SphKI/II inhibitor	Asthma	OVA-sensitized BALB/c mice	Inhibits phosphorylation of sphingosine and reduced B cell infiltration into lungs	(28)
8	FTY 720	Asthma	House dust mite model of allergic lung inflammation in C57BL/6J mice	Attenuates ORMDL3 expression	(29)
9	FTY 720	Lung cancer	Urethane-induced lung cancer in BALB/c mice	Decreased PCNA, increased caspase expression, and impaired tumor development	(33)
10	ABC294640	Lung cancer	Non-small cell lung cancer cell lines	Augmentation of antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand and upregulation of death receptor expression	(36)
11	ABC294640	Lung cancer	A549 xenografts in SCID mice	Reduced hTERT expression	(37)
12	Sphingosine	Mesothelioma	Mesothelioma cell lines	Inhibition of PKC-δ and induction of cell cycle arrest	(40)
13	JTE-013	Pulmonary hypertension (PH)	Hypoxia-mediated PH model	Prevention of development of hypoxia-mediated pulmonary hypertension	(42)
14	SKI2	PH	Hypoxia-mediated PH model in rodents	Reduced right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary remodeling	(42)
15	SKI-II	PH	Pulmonary arterial smooth muscle cells	Attenuation of hypoxia-induced increase in pulmonary arterial pressure	(45)
16	JTE-013	Hypoxic pulmonary vasoconstriction	Perfused murine lungs	Reduction in pulmonary arterial pressure	(45)
17	JTE-013	Cystic fibrosis (CF)	Lung dendritic cells	Reduced expression of MHCII and CD40	(46)
18	VPC23019	CF	Lung dendritic cells	Reduced expression of MHCII and CD40	(46)
19	LX2931	CF	Cystic fibrosis transmembrane regulator mutant mice	Increases level of S1P, normalization of the MoDC/cDC ratio, reduction in T and B cells, and normalization of pro-inflammatory cytokine levels	(50)
21	Myriocin	PF	Mouse model of radiation-induced pulmonary fibrosis	Blocks sphingolipid de novo biosynthesis and reduced level of SphK1 and serine palmitoyl transferase	(53)
22	S1P	Acute lung injury (ALI)	Conditional FOXF1 knock out mice model	Restored endothelial barrier function and decreased lung edema	(56)
23	SEW2781	ALI	LPS induced vascular leakage	Reduced vascular leakage and strengthening of endothelial barrier	(59)
24	Sphingomab	Anaphylaxis	Antigen-induced allergic response murine model	Inhibition of mast cell activation and reduction in histamines, cytokines, and chemokines	(60)
25	JTE-013	Anaphylaxis	Antigen-induced allergic response murine model	Inhibition of mast cell activation and reduction in histamines, cytokines, and chemokines	(60)
26	CYM-5442, RP-002, AAL-R	Influenza	C57BL/6 mice infected with influenza virus	Reduction in cytokine and chemokine production, inhibition of macrophage, and natural killer cell accumulation in lungs	(66)