title: CD24 activates the NLRP3 inflammasome through c-Src kinase activity in a model of the lining epithelium of inflamed periodontal tissues.
abstract: Chronic periodontitis is characterized by perturbation of the epithelial attachment to the tooth with subsequent migration of the lining epithelium and formation of a cleft or pocket. This non-keratinized lining epithelium provides initial responses to bacterial products by signalling through receptors of innate immunity to activate inflammasome pathways. These comprise an intracellular network of regulatory and effector molecules leading to synthesis and activation of pro-inflammatory cytokines. Conversely, CD24 is characteristically strongly expressed by the pocket epithelium and is reported to function as an important negative regulator for danger signals, protecting tissues from excessive leukocyte activity. The objective of the study was to determine the impact of ligation of CD24 on expression of inflammasome components. An epithelial mimic of pocket epithelium was used to evaluate activation of the NLRP3 inflammasome pathway. Surprisingly, antibody ligation of CD24 enhanced expression of NLRP3 together with co-activators ASC and caspase-1 resulting in burst release of activated interleukin (IL)-18. Potent product inhibition was detected with IL-18 suppressing expression of NLRP3, ASC, and caspase-1. Scant distribution of these products within pocket epithelium compared with healthy gingival attachment provided indication of potential cycling of NLRP3 inflammasome expression. As subjects with mild chronic periodontitis have increased titres of serum antibodies auto-reactive with CD24 compared with those of subjects with severe periodontitis, a molecular mechanism for regulated expression of the NLRP3 inflammasome mediated by c-Src kinase activity, is proposed. This pathway could be regionally disrupted by products of pathogenic bacteria with profound downregulation in the dysbiosis associated with severe disease.
authors: Department of Periodontology, School of Dentistry, Key Laboratory of Oral Biomedicine, Shandong University Shandong Province, China ; Yantai Stomatological Hospital Shandong Province, China.
authors: Wei
authors: W
authors: Guo
authors: Institute of Dental Research, Westmead Millennium Institute and Westmead Centre for Oral Health Westmead Hospital, Australia.
authors: Ping
authors: P
authors: Ye
authors: Microscopy Laboratory, Westmead Millennium Institute Westmead Hospital, Australia.
authors: Hong
authors: H
authors: Yu
authors: Yantai Stomatological Hospital Shandong Province, China.
authors: Zhonghao
authors: Z
authors: Liu
authors: Department of Periodontology, School of Dentistry, Key Laboratory of Oral Biomedicine, Shandong University Shandong Province, China.
authors: Pishan
authors: P
authors: Yang
authors: Institute of Dental Research, Westmead Millennium Institute and Westmead Centre for Oral Health Westmead Hospital, Australia ; Faculty of Dentistry, the University of Sydney Sydney, Australia.
authors: Neil
authors: N
authors: Hunter
keywords: CD24; NLRP3; inflammasome; periodontitis