Effect of locally administered Syk siRNA on allergen-induced arthritis and asthma.
New approaches for the treatment of inflammatory disorders such as rheumatic arthritis (RA) and inflammatory lung disease (asthma) are needed because a significant population of patients do not experience sustained relief with currently available therapies. The tyrosine kinase Syk plays a crucial role in inflammatory signaling pathways and has gained much attention as a potential target for treatment of inflammatory disorders. We have shown that our Syk siRNA injected directly into limb joints of arthritic mice, diminishes joint swelling and reduces levels of Syk kinase and inflammatory cytokines in joint tissue. Further, our Syk siRNA, administered via nasal instillation, inhibits recruitment of inflammatory cells to the bronchoalveolar fluid of allergen-sensitized mice. We propose that targeting Syk via localized application of Syk siRNA provides an opportunity for specific knockdown of Syk kinase with minimal potential for systemic effects.
Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, United States. zyh@dental.upenn.edu
Zhen-Yu
ZY
Huang
Moo-Kyung
MK
Kim
Tae-Hee
TH
Kim-Han
Zena K
ZK
Indik
Alan D
AD
Schreiber
D000485:Allergens / Q000276:immunology; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001249:Asthma / Q000188:drug therapy*; D015153:Blotting, Western; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D000072377:Syk Kinase; D014162:Transfection
D000485:Allergens; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse