Chemokine Receptors in Multiple Sclerosis

Szczucihski, A., Losy, J. (2007). Chemokines and chemokine receptors in multiple sclerosis. Potential targets for new therapies. Acta Neurologica Scandinavka, 115, 137-146. 

Simpson JE, Newcombe J, Cuzner ML, Woodroofe MN (1998) Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol 84 238-249 Simpson J, Rezaie P, Newcombe J, Cuzner ML, Male D, Woodroofe MN (2000) Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue. J Neuroimmunol 108 192-200... 

Sorensen TL, Sellebjerg F (2001) Distinct chemokine receptor and cytokine expression profile in secondary progressive MS. Neurology 57 1371-1376 Sorensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, Qin S, Rottman J, Sellebjerg F, Strieter RM, Frederiksen JL, Ransohoff RM (1999) Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 103 807-815... 

Simpson J, Rezaie P, Newcombe J, et al. Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue. J Neuroimmunol 2000 108 192-200. 

Table 6.8 Chemokine receptors and their ligands involved in multiple sclerosis.

Bieledd, B. et al. (2008) Treatment of multiple sclerosis with methylpredni-solone and mitoxantrone modulates the expression of CXC chemokine receptors in PBMC. Journal of Clinical Immunology, 28, 122-130. 

Mahad, D.J. et al. (2003) Longitudinal study of chemokine receptor expression on peripheral lymphocytes in multiple sclerosis CXCR3 upregulation is associated with relapse. Multiple Sclerosis (HoundmiUs, Basingstoke, Errand), 9, 189-198. 

Simpson, J. E., Newcombe, J., Cuzner, M. L., and Woodroofe, M. N. (2000b). Expression of the interferon-gamma-inducible chemokines IP-10 and Mig and their receptor, CXCR3, in multiple sclerosis lesions. Neuropathol. Appl. Neurobiol. 26, 133-142. 

Since non-psychoactive cannabinoids, such as CBD and CBN, are able to induce a marked decrease in the levels of interferons, pro-inflammatory cytokines, and chemokines after stimulation with LPS [63], this activity is unlikely to be mediated by interaction with CB receptors, while the involvement of the adenosine signaling has, rather, been postulated [64], CBD and CBG have also demonstrated a non-CB-mediated inhibition of the proliferation of human keratinocytes, supporting a potential role for cannabinoids in the treatment of psoriasis [65]. A synthetic cannabinoid, ajulemic acid (31), has been proposed for treatment of arthritis and for the management of pain and inflammation in multiple sclerosis patients [66]. 

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

Zang YC, Samanta AK, Haider JB, Hong J, Tejada-Simon MV, Rivera VM, Zhang JZ (2000) Aberrant T ceU migration toward RANTES and MIP-1 alpha in patients with multiple sclerosis. Overexpression of chemokine receptor CCR5. Brain 123(Pt 9) 1874-1882... 

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