Thursday, July 22, 2010

Proteasome inhibitor bortezomib inhibits T cell-dependent inflammatory responses - a new hope for autoimmune and inflammatory diseases?


In continuation of my update on Bortezomib, I found this info interesting to share with..
Japanese scientists lead by Dr. Koichi Yanaba, of Department of Dermatology at Nagasaki University Graduate School of Biomedical Sciences used mice to show that bortezomib, currently used to treat cancers that affect white blood cells, induces cell death only in harmful (active and proliferating) T cells, leaving the rest unharmed. If the results prove true in humans, it offers hope that this drugs or others similar to it might be used to treat inflammatory diseases without the side effects of current drugs that affect all T cells equally.
To make this discovery, scientists used two groups of mice the first treated with bortezomib and the second with saline. Researchers induced contact hypersensitivity reaction with oxazolone, a chemical allergen used for immunological experiments and found that bortezomib significantly inhibited the contact hypersensitivity responses. Results strongly suggest that bortezomib treatment enhanced T cell death by inhibiting NF-kappa B activation, which plays a key role in regulating the immune response to infection. This in turn led to the suppression of inflammatory responses in immune cells by reducing interferon-gamma production.
"We believe that this new-type remedy for autoimmune and inflammatory disease could successfully treat them in the near future", claims Dr. Koichi Yanaba...

As per the claim by the researchers, bortezomib potently inhibited CHS responses. The attenuation of CHS responses was associated with decreased inflammatory cell infiltration in the challenged skin. Specifically, bortezomib-treated mice showed significantly decreased numbers of CD4+ and CD8+ T cells in the challenged skin and draining lymph nodes. Cytoplasmic IFN-{gamma} production by CD4+ and CD8+ T cells in the draining lymph nodes was decreased substantially by bortezomib treatment. Notably, bortezomib enhanced T cell apoptosis by inhibiting NF-{kappa}B activation during CHS responses. Thus, bortezomib treatment is likely to induce T cell death, thereby suppressing CHS responses by reducing IFN-{gamma} production. These findings suggest that bortezomib treatment could be a promising strategy for treating autoimmune and inflammatory disease.

2 comments:

Sonika said...

Congrats, Dr. Umesh.
I am so happy to see a blog on this very interesting topic! Very well written, kept and illustrated.

Syn-chemist said...

Thanks for your comments. Its really interesting discussion, we had on the topic (Linkedin.). We need more discussions on such topics, so that everyone can share his/her experience and knowledge...