Chronic administration of UK-114, a multifunctional emerging protein, modulates the Th1/Th2 cytokine pattern and experimental autoimmune diseases.
UK-114 is a 14-kDa ubiquitous protein recently sequenced by several groups throughout the world. Its activity ranges from being a tumor antigen, a protein synthesis inhibitor or a specific mu-calpain activator. UK-114 shows structural homologies also with proteins of the MHC-1 binding proteins, and heat shock proteins (HSPs). We investigated the possible effects of UK-114 on T helper cells cytokine profile and the development and progression of experimental autoimmune diseases. Homogeneous recombinant UK-114 was used in all experiments. Treatment of Balb/c male mice for two weeks resulted in the increase of IL-4, and the decrease of TNF-alpha, IFN-gamma, and IL-2 release from stimulated splenocytes, suggesting that UK-114 modulates the Th1/Th2 cytokine profile toward Th2. Similar to that observed with HSP60/65, a single pretreatment of Lewis rats with UK-114 significantly blunted the development of adjuvant-induced arthritis, whereas chronic treatment of 4-week-old female NOD mice dose dependently inhibited the development of diabetes.
Department of Pharmacology, University of Milano, Italy. panerai@imiucca.csi.unimi.it
A E
AE
Panerai
P
P
Sacerdote
M
M
Bianchi
F
F
Nicoletti
B
B
Manfredi
L
L
Gaspani
A
A
Bartorelli
F
F
Ceciliani
S
S
Ronchi
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D009363:Neoplasm Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D013997:Time Factors
D016207:Cytokines; D009363:Neoplasm Proteins; C101630:UK114 antigen; D003208:Concanavalin A; D007371:Interferon-gamma