AP-1 Expression is Linked to the Pathology of Rheumatoid Arthritis

We'll start at the beginning. What is rheumatoid arthritis?

This is an excellent review of RA which can be read online.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=16190501&itool=pubmed_docsum

In brief, RA is characterized by an influx of T lymphocytes, increased blood vessel growth in the joints, and a hyperproliferation of synovial cells.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15705634&itool=pubmed_docsum

In this essay, I am going to present evidence that AP-1 signaling plays a significant role in RA pathogenesis.

The growth of new blood vessels into synovial joints has been recognized as a significant factor in the pathology of RA. In recent years, the immune hormone IL-18 was found to induce the synthesis of VEGF, vascular endothelial growth factor, thereby promoting blood vessel growth.

Curcumin inhibits the synthesis of IL-18, thereby decreasing VEGF synthesis, by inhibiting AP-1 binding activity in the nucleus.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=16368150&itool=pubmed_docsum

The human wee1 kinase induces synovial cells to go into aberrant mitosis. This is an AP-1 dependent growth response that is inhibited by curcumin.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=14534529&itool=pubmed_docsum

Currently, there are two common prescription drug treatments for RA. The first is an antibody type drug called Embrel. Embrel binds to and inhibits the activity of tumor necrosis factor, TNF, a major activator of inflammatory pathways in RA. TNF activates two genetic factors, NFKB and AP-1, which act downstream to activate TNF regulated genes.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15686622&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15013927&itool=pubmed_docsum

The second drug is methotrexate. This drug slows the growth rate and induces apoptosis in hyperproliferating synovial cells.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=12759297&itool=pubmed_docsum

RA is also associated with the breakdown of bone. Cartilage breakdown occurs as proliferating synovial cells secrete matrix metalloproteinases (MMP) , enzymes that breakdown bone, basement material and collagen.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=12759297&itool=pubmed_docsum

TNF and IL-1 both promote MMP activity which breaks down bone in osteo and rheumatoid arthritis. The induction of most MMP enzymes depend on the genetic factor AP-1.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=16148153&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=12878172&itool=pubmed_docsum

One of the current theories of RA development is the lack of apoptosis or normal cell death in the synovial cells. The survival factor survinin has been implicated in the extended life span of RA synovial cells.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15743483&itool=pubmed_docsum

Survinin synthesis is activated by NFKB.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15729715&itool=pubmed_docsum

Curcumin is well known as an inhibitor of NFKB expression and NFKB regulated genes.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=16219905&itool=pubmed_docsum

Summary.

Curcumin can inhibit both AP-1 and NFKB signaling, which is rare for a natural medicine. As such, curcumin should be used as a primary treatment for rheumatoid arthritis.

10 grams of curcumin a day dissolved in warm coconut milk or cream. 5 grams twice a day. Make it fresh each time. Purchase the curcumin bulk from the following source.

http://www.shfnatural.com. We have no financial relationship with this company.

Stay tuned...

Grouppe Kurosawa, Medicine in the Public Interest
(http://www.grouppekurosawa.com)