Antisense-mediated inhibition of ICAM-1 expression: a therapeutic strategy against inflammation of human periodontal tissue.
Periodontal diseases, such as gingivitis and periodontitis, are caused by a mixed infection by several types of bacteria in the dental plaque, causing a chronic inflammation of the gingival mucosa. Inflammatory processes in conjunction with immune responses to bacterial attacks are generally protective. In profound periodontitis, however, hyperresponsiveness and hypersensitivity of the immune system are counterproductive because of the destruction of the affected periodontal connective tissues. The intercellular adhesion molecule type 1 (ICAM-1) plays a key role in the onset and manifestation of inflammatory responses. Thus, inhibition of ICAM-1 expression could be of therapeutic relevance for the treatment of destructive periodontitis. Here, antisense oligonucleotides (AS-ON) directed against ICAM-1 suppress protein expression and mRNA levels specifically and effectively in primary human endothelial cells of different tissue origin. Moreover, downregulation of ICAM-1 expression is also observed in AS-ON-transfected inflamed gingival mucosal tissue of patients with periodontal diseases. This work strongly suggests exploiting the local topical application of ICAM-1-directed AS-ON as a therapeutic tool against inflammatory processes of the human gingiva.
Nedbal
Wolfgang
W
A3D GmbH-Antisense Design and Drug Development, Heidelberg, Germany. nedbal@a3d-heidelberg.de
Tomakidi
Pascal
P
Lehmann
Maik Jorg
MJ
Dörfer
Christof
C
Kohl
Annette
A
Sczakiel
Georg
G
D001483:Base Sequence; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D005891:Gingivitis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D009061:Mouth Mucosa / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D010518:Periodontitis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018836:Inflammation Mediators; D007375:Interleukin-1; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1