Inhibition of intracellular cathepsin activities and suppression of immune responses mediated by helper T lymphocyte type-2 by peroral or intraperitoneal administration of vitamin B6.
We reported that pyridoxal phosphate (PAP), a coenzyme form of vitamin B6, strongly inhibits activities of cathepsin B and weakly inhibits those of cathepsins S, K, and C in vitro. Either intraperitoneal injection or peroral administration of medication doses of vitamin B6 in the diet caused dose-dependent inhibition of hepatic cathepsins B, L, S, and C, and the inhibition was exhibited much more significantly in the case of a high protein diet than in a low protein diet. Administration of vitamin B6 induced the suppression of immune responses against ovalbumin (OVA) mediated by helper T lymphocyte type-2, based on the suppression of antigen processing by cathepsin B inhibition, as in the case of CA-074 administration, a cathepsin B specific inhibitor. Ovalbumin-dependent production of immunoglobulins IgE, IgG1 and interleukin IL-4 was suppressed by administration of medication doses of pyridoxal (PA) or pyridoxine (PI), while the production of IgG2alpha and interferon (INF)-gamma mediated by helper T lymphocyte type 1 was not changed. Administration of medication doses of vitamin B6 caused the inhibition of intracellular cathepsin B activity due to suppression of the functions of helper T lymphocyte type-2.
Katunuma
N
N
Tokushima Bunri University, Institute for Health Sciences, Japan.
Matsui
A
A
Endo
K
K
Hanba
J
J
Sato
A
A
Nakano
M
M
Yuto
Y
Y
Tada
Y
Y
Asao
T
T
Himeno
K
K
Maekawa
Y
Y
Inubushi
T
T
D000284:Administration, Oral; D000818:Animals; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D007136:Immunoglobulins / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011730:Pyridoxal / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D011736:Pyridoxine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*
D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D011480:Protease Inhibitors; D011730:Pyridoxal; D011732:Pyridoxal Phosphate; D002403:Cathepsins; D011736:Pyridoxine