Inhibition of mitogenic stimulant-induced activation of thymocytes with zinc tetrakis-(N-methyl-4'-pyridyl) porphyrinato.
Zinc porphyrins have anti-inflammatory and anti-allergic properties. The objective of the present study was to characterize the mechanism of zinc tetrakis-(N-methyl-4'-pyridyl) porphyrinato (ZnTMPyP) immune modulation by investigating its effects on the proliferative activity during thymocyte stimulation with mitogenic factors and the molecular events mediating thymocyte proliferation. The results indicate that ZnTMPyP inhibited thymocyte proliferation stimulated with various mitogenic factors, such as concanavalin A (Con A), interleukin (IL)-1beta, and lipopolysaccharide-exposed macrophage supernatant, in a concentration-dependent manner. ZnTMPyP was also effective in preventing DNA binding activity of nuclear factor kappaB (NF-kappaB) and IL-2 production by thymocytes in response to Con A or IL-1beta. Inhibition of p38 mitogen-activated protein kinase (MAPK) with SB203580 substantially inhibited Con A- or IL-1beta-induced DNA binding activity of NF-kappaB, whereas ZnTMPyP inhibited the activation of p38 MAPK. ZnTMPyP also inhibited Con A-induced chemiluminescence and tyrosine phosphorylation by thymocytes. In conclusion, our findings suggest that the antiproliferative effect of ZnTMPyP may be mediated by effective inhibition of the production of reactive oxygen species, tyrosine phosphorylation, p38 MAPK activation, NF-kappaB activation, and IL-2 production during mitogenic stimulation of thymocytes.
Kang
Jihee Lee
JL
Department of Physiology, College of Medicine, Division of Cell Biology, Ewha Medical Research Center and Ewha Womans University, Seoul, Korea.
Lee
Hui Su
HS
Jung
Hae Jin
HJ
Kim
Hee Jae
HJ
Hah
Jong Sik
JS
Castranova
Vincent
V
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D006131:Growth Inhibitors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008934:Mitogens / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D008665:Metalloporphyrins; D008934:Mitogens; C060088:zinc tetra(4-N-methylpyridyl)porphine; D015032:Zinc