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The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases pp 169–191Cite as

Roles of Ceramides and Other Sphingolipids in Immune Cell Function and Inflammation

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1161))

Abstract

Ceramides are bioactive sphingolipids that support the structure of the plasma membrane and mediate numerous cell-signaling events in eukaryotic cells. The finding that ceramides act as second messengers transducing cellular signals has attracted substantial attention in several fields of Biology. Since all cells contain lipid plasma membranes, the impact of various ceramides, ceramide synthases, ceramide metabolites, and other sphingolipids has been implicated in a vast range of cellular functions including, migration, proliferation, response to external stimuli, and death. The roles of lipids in these functions widely differ among the diverse cell types. Herein, we discuss the roles of ceramides and other sphingolipids in mediating the function of various immune cells; particularly dendritic cells, neutrophils, and macrophages. In addition, we highlight the main studies describing effects of ceramides in inflammation, specifically in various inflammatory settings including insulin resistance, graft-versus-host disease, immune suppression in cancer, multiple sclerosis, and inflammatory bowel disease.

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Abbreviations

3KS:

3-keto-sphinganine

acyl-CoA:

fatty acyl-coenzyme A

aSMase:

acid sphingomyelinase

ATM:

adipose tissue macrophages

C1P:

ceramide 1-phosphate

CerS:

ceramide synthases

CNS:

central nervous system

COX-2:

cyclooxygenase-2

CTL:

cytotoxic T lymphocytes

CXCR2:

C-X-C motif chemokine receptor type 2

DAG:

diacylglycerol

DC:

dendritic cells

DSS:

dextran sulfate sodium

EAE:

autoimmune encephalomyelitis

ERK:

extracellular signal-regulated kinases

fMLP:

N-formylmethionine-leucyl-phenylalanine

GalCer:

galactosylceramides

G-CSF:

granulocyte-colony stimulating factor

GI:

gastrointestinal

GVHD:

Graft-Versus-Host Disease

HIV:

human immunodeficiency virus

IBD:

Inflammatory Bowel Disease

IFNγ:

interferon gamma

IL-:

interleukin

iNOS:

inducible nitric oxide synthase

IRS-1:

insulin receptor substrate-1

JNK:

c-Jun N-terminal kinase

LacCer:

lactosylceramide

LipC6:

nanoliposome-loaded C6-ceramide

LPS:

lipopolysaccharide

MAPK:

mitogen-activated protein kinase

M-CSF:

macrophage-colony stimulating factor

MDSC:

myeloid-derived suppressor cells

MS:

Multiple Sclerosis

NETs:

neutrophil extracellular traps

Nlrp3:

Nod-like receptor pyrin domain-containing-3

NO:

nitric oxide

PI3K:

phosphatidylinositol 3 kinase

PKB:

protein kinase B

PKCζ:

protein kinase C zeta

PRR:

pattern recognition receptors

ROS:

reactive oxygen species

S1P:

sphingosine 1-phosphate

Sa:

sphinganine

SK:

sphingosine kinase

SLs:

sphingolipids

SMase:

sphingomyelinase

So:

sphingosine

SPT:

serine palmitoyltransferase

TAM:

tumor-associated macrophages

TCR:

T cell receptor

TEM:

tumor microenvironment

TGFβ:

transforming growth factor beta

TLRs:

toll-like receptor

TNFα:

tumor necrosis factor alpha

Treg:

regulatory CD4+ T cells

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Acknowledgements

The authors are indepted to Ms. Yara Khodour for her diligent redrawing of Fig. 15.2 and her full chapter proof. Dr. Johnny Stiban acknowledges the receipt of two grants from Birzeit University that allowed him to pursue this endeavor (Grant #240193 and #241109).

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Authors and Affiliations

  1. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Sabrin Albeituni

  2. Department of Biology and Biochemistry, Birzeit University, West Bank, Palestine

    Johnny Stiban

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  1. Sabrin Albeituni
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  2. Johnny Stiban
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  1. 431 Chemistry Building, Wayne State University, Detroit, MI, USA

    Kenneth V. Honn

  2. National Institutes of Health, Durham, NC, USA

    Darryl C. Zeldin

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Albeituni, S., Stiban, J. (2019). Roles of Ceramides and Other Sphingolipids in Immune Cell Function and Inflammation. In: Honn, K., Zeldin, D. (eds) The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases. Advances in Experimental Medicine and Biology, vol 1161. Springer, Cham. https://doi.org/10.1007/978-3-030-21735-8_15

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