TY - CHAP
T1 - Complement C3 as a target of host modulation in periodontitis
AU - Hajishengallis, George
AU - Kajikawa, Tetsuhiro
AU - Hajishengallis, Evlambia
AU - Maekawa, Tomoki
AU - Li, Xiaofei
AU - Belibasakis, George N.
AU - Bostanci, Nagihan
AU - Mastellos, Dimitrios C.
AU - Yancopoulou, Despina
AU - Hasturk, Hatice
AU - Lambris, John D.
N1 - Publisher Copyright:
© Springer Nature Switzerland AG 2020.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Although originally identified as a blood-based antimicrobial system, complement is now regarded as a central regulator of immune and inflammatory responses and tissue homeostasis. When dysregulated or overactivated, however, complement can turn from a homeostatic to a pathological effector that drives a number of inflammatory disorders. In this context, destructive periodontal inflammation in humans is correlated with elevated complement activity. Moreover, mechanistic studies in mice have causally linked the central complement component C3 and downstream signaling pathways in the induction of periodontal dysbiosis and inflammation that leads to alveolar bone loss. Consistent with this, pharmacological inhibition of C3 activation by a locally administered drug (Cp40/AMY-101) was shown to suppress both induced and naturally occurring periodontitis in non-human primates. Thus, C3-targeted intervention represents a promising host-modulation approach to treat human periodontitis.
AB - Although originally identified as a blood-based antimicrobial system, complement is now regarded as a central regulator of immune and inflammatory responses and tissue homeostasis. When dysregulated or overactivated, however, complement can turn from a homeostatic to a pathological effector that drives a number of inflammatory disorders. In this context, destructive periodontal inflammation in humans is correlated with elevated complement activity. Moreover, mechanistic studies in mice have causally linked the central complement component C3 and downstream signaling pathways in the induction of periodontal dysbiosis and inflammation that leads to alveolar bone loss. Consistent with this, pharmacological inhibition of C3 activation by a locally administered drug (Cp40/AMY-101) was shown to suppress both induced and naturally occurring periodontitis in non-human primates. Thus, C3-targeted intervention represents a promising host-modulation approach to treat human periodontitis.
KW - AMY-101
KW - Bone loss
KW - C3
KW - Complement
KW - Compstatin
KW - Host modulation
KW - Inflammation
KW - Periodontitis
KW - Therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85089334420&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089334420&partnerID=8YFLogxK
U2 - 10.1007/978-3-030-42990-4_2
DO - 10.1007/978-3-030-42990-4_2
M3 - Chapter
AN - SCOPUS:85089334420
SN - 9783030429898
SP - 13
EP - 29
BT - Emerging Therapies in Periodontics
PB - Springer International Publishing
ER -