title: Endogenous sulfur dioxide is a novel adipocyte-derived inflammatory inhibitor.
abstract: The present study was designed to determine whether sulfur dioxide (SO2) could be endogenously produced in adipocyte and served as a novel adipocyte-derived inflammatory inhibitor. SO2 was detected in adipose tissue using high-performance liquid chromatography with fluorescence detection. SO2 synthase aspartate aminotransferase (AAT1 and AAT2) mRNA and protein expressions in adipose tissues were measured. For in vitro study, 3T3-L1 adipocytes were cultured, infected with adenovirus carrying AAT1 gene or lentivirus carrying shRNA to AAT1, and then treated with tumor necrosis factor-α (TNF-α). We found that endogenous SO2/AAT pathway existed in adipose tissues including perivascular, perirenal, epididymal, subcutaneous and brown adipose tissue. AAT1 overexpression significantly increased SO2 production and inhibited TNF-α-induced inflammatory factors, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) secretion from 3T3-L1 adipocytes. By contrast, AAT1 knockdown decreased SO2 production and exacerbated TNF-α-stimulated MCP-1 and IL-8 secretion. Mechanistically, AAT1 overexpression attenuated TNF-α-induced IκBα phosphorylation and degradation, and nuclear factor-κB (NF-κB) p65 phosphorylation, while AAT1 knockdown aggravated TNF-α-activated NF-κB pathway, which was blocked by SO2. NF-κB inhibitors, PDTC or Bay 11-7082, abolished excessive p65 phosphorylation and adipocyte inflammation induced by AAT1 knockdown. This is the first report to suggest that endogenous SO2 is a novel adipocyte-derived inflammatory inhibitor.
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Research Center, Peking University First Hospital, Beijing 100034, China.
authors.forename: Dingfang
authors.initials: D
authors.lastname: Bu
authors.affiliation: University of California, San Diego, La Jolla, California, 92093, United States of America.
authors.forename: Selena
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China.|Key Lab. of Ministry of Education of China, Beijing, China.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.|Key Lab. of Ministry of Education of China, Beijing, China.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D013458:Sulfur Dioxide / Q000378:metabolism*; D013859:Thiocarbamates / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016209:Interleukin-8; D007527:Isoenzymes; D009570:Nitriles; D034741:RNA, Small Interfering; C498144:Rela protein, mouse; D013450:Sulfones; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D013458:Sulfur Dioxide; C066229:prolinedithiocarbamate; D000072000:NF-KappaB Inhibitor alpha; D011392:Proline; D001219:Aspartate Aminotransferases