Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease

Table 1

Potential harmful and beneficial mechanisms of Cer and S1P in IBD.

SLs	Effect	Target	Tissue/cells	References
Harmful
Cer	Increases	NF-κB & COX-2	Intestinal tract	[12, 13]
		BCL-2 expression	Intestinal tract	[12, 13]
		Inflammation	Intestinal tract	[12, 13]
	Decreases	Apoptosis	Intestinal tract	[12, 13]
		Expression of BAX, BAK & BAD	Intestinal tract	[12, 13]
Cer	Activates	Immune cells	Intestinal tract	[14–16]
		MAPK cascade	Intestinal tract	[17]
	Decreases	Cholesterol levels	IEC tight junctions	[20, 21]
		Barrier function	IECs	[20, 21]
SMase	Increases	TNF-α, IL-1β  & IL-6 secretion	Intestinal macrophages	[22]
		LPS-induced TNF-α release	PBMCs	[22]
		TNF-α, IL-1β  & IL-6 levels in DSS-induced colitis	Colon	[22]
		LPS-induced increase of Cer & NF-κB	Intestinal macrophages	[22]
		Inflammation	Colon	[22]
		LPS-induced cell death	Intestinal tract	[22]
nCDase	Decreases	DSS-induced S1P and COX-2 levels	Colon	[23]
		Endotoxin levels	Serum	[23]
Dietary SM	Increases	DSS-induced inflammation	Colon	[24, 25]
		Cathepsin D activity, BID activation, HT-29 cell & IEC apoptosis	Colon	[24, 25]
	Decreases	BCL-2 levels	Colon	[24, 25]
Beneficial
Cer	Decreases	IL-6 synthesis; Mast cell degranulation	Colon	[26]
Alkaline SMase	Decreases	PAF	Intestinal tract	[16]
		DSS-induced inflammation	Rectum	[27]
		Tumor incidence	Colon	[28]
		DSS + azoxymethane cancer aggressiveness	Colon	[28]
	Protects		Colonic epithelium	[29]
Acidic SMase	Increases	Apoptosis	Colon cancer cells	[30]
Dietary SM	Decreases	DSS-induced inflammation	Colon	[29]
		Lymphocyte entry	Colon, PPAR-γ^−/− mice	[31]
		Carcinoma burden	Colon, PPAR-γ^−/− mice	[31]
		F4/80^+ macrophages	Mesenteric lymph node	[31]
	Delays; Hastens	Inflammation	Intestinal tract	[31]
		Recovery	Intestinal tract	[31]
	Increases	Survival of PPAR-γ^−/− mice		[31]
		Chemokines and their receptors	Intestinal tract, PPAR-γ^−/− mice	[31]
		CD4^+ T cell maturation genes	Intestinal tract, PPAR-γ^−/− mice	[31]
S1P	Increases	B & T cell survival	Intestinal tract	[26]
	Decreases	T cell proliferation; Cytokine synthesis	Intestinal tract	[26]
S1P	Increases	COX-2 & PGE2, inflammation, metalloproteinase production	Intestinal tract	[32, 33]