Therapeutic uses of glandular kallikrein

Abstract

An immunosuppressive peptide of 40 kDa molecular weight, isolated from the submandibular glands (SMG*) of rats, had the capacity to suppress immune reactions upon parenteral administration to rats and mice. The peptide was identified as glandular kallikrein (K1) by partial sequencing and by enzymatic activity. Further experiments revealed that the excision of SMG (SMGx) from Lewis rats prevents the oral induction of immunological tolerance against native bovine type II collagen (BCII). Thus SMGx rats, when they were given oral BCII and were subsequently immunized with the same antigen, developed collagen induced arthritis (CA), while normal rats given an identical treatment were protected from the disease. When SMGx rats were orally given porcine K1 in conjunction with BCII, the capacity of such animals to develop oral tolerance was fully restored. These results indicate that normal SMG function is required for induction of oral tolerance and that K1 is involved in mediating this function.

Description

PRIOR APPLICATION [0001] This application is a Divisional of U.S. Ser. No. 10 / 162,697 filed Jun. 6, 2002 which claims priority under 35 USC § 119(e) to U.S. Ser. No. 60 / 296,153, filed Jun. 7, 2001, the disclosures of which are incorporated herein by reference.BACKGROUND OF THE INVENTION [0002] Kallikreins belong to a family of serine proteases capable of cleaving various substrates and generating biologically active peptides. In spite of the names, tissue or glandular kallikreins should be distinguished from plasma kallikrein. They differ from plasma kallikrein in their genes of origin, molecular weight, amino acid sequences, substrates, peptide products and most probably physiological functions. There are at least 20 genes for tissue kallikrein in rodents (98), while in humans 15 genes have been so far described (Yousef, G. M., Scorilas, A., Jung, K., Ashworth, L. K., Diamondis, E. P. J. Biol. Chem. 2001, 276:53-61; Clements, J., Hooper, J., Dong, Y., Harvey, T. Biol. Chem. 2001, 3...

AI Technical Summary

Benefits of technology

"The patent describes a pharmaceutical composition that includes glandular kallikrein and an antigen, which can be used to treat autoimmune diseases in animals. The composition can reduce the animal's immune response to the antigen and can also be used to enhance the immune response to orally administered antigens. The patent also describes a method of inducing tolerance to the antigen by administering glandular kallikrein to the animal. Overall, the patent provides a technical solution for developing new treatments for autoimmune diseases in animals."

Problems solved by technology

While the action of GK on kininogen is particularly well studied, the full range of GK substrates has not yet been investigated.

Images