Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells.
T cells produce a number of cytokines and chemokines upon stimulation with TLR agonists in the presence or absence of TCR signals. Here, we show that secretion of neutrophil chemoattractant CXCL8 from human T cell line Jurkat in response to stimulation with TLR agonists is reduced when cell stimulation is carried out in presence of serum. Serum does not, however, inhibit TCR-activated secretion of CXCL8 nor does it down-regulate TLR-costimulated IL-2 secretion from activated T cells. The molecule that can mimic the ability to bring about suppression in CXCL8 from TLR-activated T cells is serum-borne bioactive lipid, S1P. Serum and S1P-mediated inhibition require intracellular calcium. S1P also suppresses CXCL8 secretion from peripheral blood-derived human T cells activated ex vivo with various TLR ligands. Our findings reveal a previously unrecognized role for S1P in regulating TLR-induced CXCL8 secretion from human T cells.
Aruna Asaf Ali Marg, New Delhi, India.
Naveen
N
Sharma
Ajay Suresh
AS
Akhade
Ayub
A
Qadri
D002118:Calcium / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D005408:Flagellin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D055666:Lipopeptides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008246:Lysophospholipids / Q000494:pharmacology*; D018716:Molecular Mimicry; D010069:Oxadiazoles / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D044967:Serum / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013876:Thiophenes / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000235:genetics* / Q000276:immunology; D020298:U937 Cells
C508606:CXCL8 protein, human; D007376:Interleukin-2; D016209:Interleukin-8; D055666:Lipopeptides; D008246:Lysophospholipids; D010069:Oxadiazoles; C508075:Pam(3)CSK(4) peptide; D011409:Propylene Glycols; D011948:Receptors, Antigen, T-Cell; C503964:SEW2871; D013876:Thiophenes; D051193:Toll-Like Receptors; D005408:Flagellin; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D002118:Calcium