Tryptase activates peripheral blood mononuclear cells causing the synthesis and release of TNF-alpha, IL-6 and IL-1 beta: possible relevance to multiple sclerosis.
Presence of mast cells and an increase in the concentration of their products has been reported in multiple sclerosis (MS) plaques. The most abundant secretory mediator of the human mast cell is the tetrameric protease tryptase. We demonstrate that tryptase can activate peripheral mononuclear cells (PBMCs), isolated from healthy donors as well as MS patients for the release of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta. Cytokine secretion was significantly higher in secondary progressive (SP) MS patients and healthy control (HC) individuals than in relapsing-remitting (RR) patients. Our findings suggest that tryptase is, most probably, an important mediator of inflammation in MS.
Malamud
Vivian
V
Department of Cellular Biochemistry and Human Genetics, Hebrew University, Hadassah Medical School, P.O. Box 12272, 91120 Jerusalem, Israel.
Vaaknin
Ady
A
Abramsky
Oded
O
Mor
Michal
M
Burgess
Laurence E
LE
Ben-Yehudah
Ahmi
A
Lorberboum-Galski
Haya
H
D000328:Adult; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000502:physiology*; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D012697:Serine Endopeptidases; D053802:Tryptases