David Naor, Lora Eshkar Sebban, Keren Or Amar and Shmuel Cohen
The Lautenberg Center for Immunology and Cancer Research, IMRIC, The Hebrew University- Hadassah Medical School, Jerusalem 91120, Israel
A human CD44-derived 5-mer peptide displays an efficient anti-inflammatory response in collagen– induced arthritis mouse model, as it can regenerate the normal anatomy and the function of the damaged tissue. Injection of the peptide after the onset of the disease substantially reduced the inflammation as indicated by blind analysis of footpad swelling and histopathology of joint sections. The effect is autoimmune-specific and the peptide injection does not induce neutralizing antibodies. In attempt to understand its mechanism of action we focused efforts to identify the target molecule of this 5-mer peptide. Mass Spectrometry analysis revealed a protein epitope as a potential target for the anti-inflammatory activity of the 5-mer peptide. The protein containing the epitope, which is recognized and neutralized by the peptide, is highly involved not only in the pathology of rheumatoid arthritis, but also in the pathologies of Alzheimer's disease, cancer diseases and cardiovascular diseases. This finding provides additional indications for the therapeutic potential of the 5-mer peptide. The protein containing the target epitope strongly supports cell migration in a rheumatoid arthritis model. This finding can explain why the 5-mer peptide is effective in the inhibition of joint inflammation and regeneration of joint normal tissue, as cell migration is an essential element of the inflammation cascade.