title: Caspase-12 silencing attenuates inhibitory effects of cigarette smoke extract on NOD1 signaling and hBDs expression in human oral mucosal epithelial cells.
abstract: Cigarette smoke exposure is associated with increased risk of various diseases. Epithelial cells-mediated innate immune responses to infectious pathogens are compromised by cigarette smoke. Although many studies have established that cigarette smoke exposure affects the expression of Toll-liked receptor (TLR), it remains unknown whether the nucleotide-binding oligomerization domain-containing protein 1 (NOD1) expression is affected by cigarette smoke exposure. In the study, we investigated effects of cigarette smoke extract (CSE) on NOD1 signaling in an immortalized human oral mucosal epithelial (Leuk-1) cell line. We first found that CSE inhibited NOD1 expression in a dose-dependent manner. Moreover, CSE modulated the expression of other crucial molecules in NOD1 signaling and human β defensin (hBD) 1, 2 and 3. We found that RNA interference-induced Caspase-12 silencing increased NOD1 and phospho-NF-κB (p-NF-κB) expression and down-regulated RIP2 expression. The inhibitory effects of CSE on NOD1 signaling can be attenuated partially through Caspase-12 silencing. Intriguingly, Caspase-12 silencing abrogated inhibitory effects of CSE on hBD1, 3 expression and augmented induced effect of CSE on hBD2 expression. Caspase-12 could play a vital role in the inhibitory effects of cigarette smoke on NOD1 signaling and hBDs expression in oral mucosal epithelial cells.
authors.affiliation: Department of Oral Medicine, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China; Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oral Medicine, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Ya-jie
authors.initials: YJ
authors.lastname: Qian
authors.affiliation: Department of Endodontics, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Oral Medicine, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Oral Medicine, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Duan
authors.affiliation: Department of Oral Pathology, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Department of Endodontics, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Zhu
authors.affiliation: Department of Oral Medicine, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China.
authors.forename: Wei-yun
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China.
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Han
authors.affiliation: Department of Oral Medicine, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, China.
authors.forename: Wen-mei
authors.initials: WM
authors.lastname: Wang
mesh_terms: D053454:Caspase 12 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D009061:Mouth Mucosa / Q000187:drug effects; D053474:Nod1 Signaling Adaptor Protein / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000235:genetics; D062789:Tobacco Products / Q000633:toxicity; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C106641:DEFB4A protein, human; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D023083:beta-Defensins; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053454:Caspase 12