Objective:To study the relationship between the single nucleotide polymorphisms(SNPs)of IFNGR2genes(rs9808753,rs11910627 and rs1532) and IL-12 B gene(rs2288831)and the susceptibility to hand,foot and mouth disease(HFM...Objective:To study the relationship between the single nucleotide polymorphisms(SNPs)of IFNGR2genes(rs9808753,rs11910627 and rs1532) and IL-12 B gene(rs2288831)and the susceptibility to hand,foot and mouth disease(HFMD)caused by enterovirus 71(EV71).Methods:Blood samples were collected from 145 HFMD children infected by EV71,104 children with EV71 covert infection,and 89 normal control children,followed by DNA extraction.IFNGR2 and IL-12 Bpolymorphisms were detected by imLDRTM.Results:Compared with the control group,IFNGR2rs9808753 genotype and allele distributions of EV71-infected group and EV71 covert infection group showed significant differences(P<0.05).A allele frequency in EV71-infected patients and covert EV71-infected patients was higher than that in the control group(P <0.05).While the genotype and allele frequencies of rs2288831 in IL-12 B did not show significant difference between EV71-infected groups and healthy controls.Conclusion:These findings suggested that the single nucleotide polymorphism of IFNGR2 gene site rs9808753(A/G)was associated with the susceptibility to EV71-infection,and A allele of rs9808753 might be one potential genetic susceptibility factor of EV71-infection.While the rs2288831(C/T)polymorphism of IL-12 Bdid not correlate with the susceptibility of EV71-infection.展开更多
Fatty acid metabolism mediates macrophage function;however,the underlying mechanism by which fatty acid metabolism regulates macrophage interleukin(IL)-1βproduction remains to be uncovered.Here,we used genome-wide as...Fatty acid metabolism mediates macrophage function;however,the underlying mechanism by which fatty acid metabolism regulates macrophage interleukin(IL)-1βproduction remains to be uncovered.Here,we used genome-wide association studies(GWAS)to identify several porcine serum IL-1β-related genes,such as the fatty acid metabolizing enzyme acyl-CoA thioesterase 11(ACOT11).We then demonstrated that inflammatory macrophages have low expression of ACOT11,and ACOT11 overexpression inhibits IL-1βmaturation from inflammatory macrophages.Mechanistically,ACOT11 promotes intracellular fatty acids accumulation,including eicosatetraenoic acid(EA)and stearic acid(SA),which inhibit activation of the Janus kinase(JAK)—signal transducer and activator of transcription(STAT)signaling through palmitoylation of interferon(IFN)-γreceptor(IFNGR)2 at C261site.Furthermore,we also found that EA attenuates lipopolysaccharide(LPS)-induced sepsis in mice.Collectively,our findings reveal a mechanism involving ACOT11-mediated post-translational modification that regulates macrophage function and provide a promising therapeutic target for the treatment of inflammatory diseases associated with macrophages.展开更多
基金funded by National Natural Science Foundation of China(No.81460251)Appropriate technology research and development project of Guangxi Medical and Health(No.S20141401)Chairman Foundation of Guangxi(No.201417)
文摘Objective:To study the relationship between the single nucleotide polymorphisms(SNPs)of IFNGR2genes(rs9808753,rs11910627 and rs1532) and IL-12 B gene(rs2288831)and the susceptibility to hand,foot and mouth disease(HFMD)caused by enterovirus 71(EV71).Methods:Blood samples were collected from 145 HFMD children infected by EV71,104 children with EV71 covert infection,and 89 normal control children,followed by DNA extraction.IFNGR2 and IL-12 Bpolymorphisms were detected by imLDRTM.Results:Compared with the control group,IFNGR2rs9808753 genotype and allele distributions of EV71-infected group and EV71 covert infection group showed significant differences(P<0.05).A allele frequency in EV71-infected patients and covert EV71-infected patients was higher than that in the control group(P <0.05).While the genotype and allele frequencies of rs2288831 in IL-12 B did not show significant difference between EV71-infected groups and healthy controls.Conclusion:These findings suggested that the single nucleotide polymorphism of IFNGR2 gene site rs9808753(A/G)was associated with the susceptibility to EV71-infection,and A allele of rs9808753 might be one potential genetic susceptibility factor of EV71-infection.While the rs2288831(C/T)polymorphism of IL-12 Bdid not correlate with the susceptibility of EV71-infection.
基金supported by the National Natural Science Foundation of China(32225047)Double first-class discipline promotion project(2023B10564001)+2 种基金Open Project Program of Sichuan Provincial Key Laboratory of Animal Disease-resistant Nutrition,Sichuan Agricultural University(SZ202301-02)Guangdong Basic and Applied Basic Research Foundation(2022A1515111229)Hainan Provincial Natural Science Foundation of China(325QN483).
文摘Fatty acid metabolism mediates macrophage function;however,the underlying mechanism by which fatty acid metabolism regulates macrophage interleukin(IL)-1βproduction remains to be uncovered.Here,we used genome-wide association studies(GWAS)to identify several porcine serum IL-1β-related genes,such as the fatty acid metabolizing enzyme acyl-CoA thioesterase 11(ACOT11).We then demonstrated that inflammatory macrophages have low expression of ACOT11,and ACOT11 overexpression inhibits IL-1βmaturation from inflammatory macrophages.Mechanistically,ACOT11 promotes intracellular fatty acids accumulation,including eicosatetraenoic acid(EA)and stearic acid(SA),which inhibit activation of the Janus kinase(JAK)—signal transducer and activator of transcription(STAT)signaling through palmitoylation of interferon(IFN)-γreceptor(IFNGR)2 at C261site.Furthermore,we also found that EA attenuates lipopolysaccharide(LPS)-induced sepsis in mice.Collectively,our findings reveal a mechanism involving ACOT11-mediated post-translational modification that regulates macrophage function and provide a promising therapeutic target for the treatment of inflammatory diseases associated with macrophages.
