title: Superantigen staphylococcal enterotoxin C1 mutant can reduce paraquat pulmonary fibrosis.
abstract: A network of inflammation factors is related to pulmonary fibrosis induced by paraquat (PQ) poisoning. At high doses, the superantigen staphylococcal enterotoxin C1 (SEC1) can induce immunological unresponsiveness and inhibit release of inflammation factors. In this study, site-directed mutagenesis was performed at the H118 and H122 amino acid residues of SEC1 to reduce SEC1 toxicity. The SEC1 mutant showed significantly decreased pyrogenic toxicity, but retained clonal anergy at high dosages in vitro. Pretreatment with the SEC1 mutant prior to PQ poisoning in mice reduced symptom duration and severity, prolonged survival time, and decreased the splenocyte response to ConA induction. The SEC1 mutant also down-regulated several important cytokines related to fibrosis in the plasma after PQ poisoning. SEC1 decreased the expression of genes related to pulmonary fibrosis, including α-SMA, COL1a1, COL3 and TGF-β1, in PQ poisoned mice. Histomorphological observation indicated alleviation of pathological changes in the lungs after SEC1 pretreatment compared to mice in the PQ group. In conclusion, the SEC1 mutant reduced pulmonary interstitial fibrosis induced by PQ poisoning.
authors.affiliation: a Emergency Department , Shengjing Hospital of China Medical University , Shenyang , P.R. China .
authors.forename: Tiegang
authors.initials: T
authors.lastname: Li
authors.affiliation: b Institute of Applied Ecology, Chinese Academy of Sciences , Shenyang , P.R. China , and.
authors.forename: Mingkai
authors.initials: M
authors.lastname: Xu
authors.affiliation: c Endocrinology Department , Shengjing Hospital of China Medical University , Shenyang , P.R. China.
authors.forename: Nana
authors.initials: N
authors.lastname: Wang
authors.affiliation: a Emergency Department , Shengjing Hospital of China Medical University , Shenyang , P.R. China .
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000627:therapeutic use* / Q000633:toxicity; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004768:Enterotoxins / Q000235:genetics / Q000627:therapeutic use* / Q000633:toxicity; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006540:Herbicides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control*; D011817:Rabbits; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D018089:Superantigens; D016019:Survival Analysis
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D004768:Enterotoxins; D006540:Herbicides; D018089:Superantigens; C034959:enterotoxin C, staphylococcal; D010269:Paraquat
keywords: Paraquat; pulmonary fibrosis; staphylococcal enterotoxin C1; superantigen