Targeting the glycoprotein 130 receptor subunit to control pain and inflammation.
The glycoprotein 130 (gp130) is a shared signal-transducing-membrane-associated receptor for several hematopoietic cytokines. Its activation is implicated in pain and in a variety of diseases via signaling of proinflammatory cytokines. These include interleukin-6 (IL-6) subfamily cytokines, many of which play important roles in the pathogenesis of diseases such as rheumatoid arthritis, Castleman's disease, and Kaposi's sarcoma. Several strategies have been developed to block gp130-receptor-mediated signaling. These include the application of monoclonal antibodies, the creation of mutant form(s) of the gp130 with increased binding affinity for such ligands as IL-6/sIL-6R complex, and the generation of antagonists by selective mutagenesis of the specific cytokine/gp130 receptor binding site(s). Other strategies include targeting gp130-mediated signaling pathways such as that involving signal transducer and activator of transcription-3. This review provides a summary of the latest research pertaining to the role of gp130 in the pathogenesis of inflammatory and other diseases in which the gp130 receptor is implicated. An overview of antagonists targeting the gp130 receptor is included with particular emphasis on their mechanism of action and their limitations and potential for therapeutic application.
Jazayeri
Jalal A
JA
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Melbourne, Australia. jalal.jazayeri@pharm.monash.edu.au
Upadhyay
Aradhana
A
Vernallis
Ann B
AB
Carroll
Graeme J
GJ
D000818:Animals; D050822:Cytokine Receptor gp130 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016207:Cytokines; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; D021122:Protein Subunits; D050822:Cytokine Receptor gp130