Objective S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities.We previously reported that S100A11 was differentially expressed in the respirator...Objective S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities.We previously reported that S100A11 was differentially expressed in the respiratory tracts of asthmatic rats as compared with normal controls.Here,we aimed to analyze the potential of S100A11 to regulate both allergen-induced airway hyperresponsiveness(AHR)as well as acetylcholine(ACh)-induced hypercontractility of airway smooth muscle(ASM)and contraction of ASM cells(ASMCs).Methods Purified recombinant rat S100A11 protein(rS100A11)was administered to OVA-sensitized and challenged rats and then the AHR of animals was measured.The relaxation effects of rS100A11 on ASM were detected using isolated tracheal rings and primary ASMCs.The expression levels of un-phosphorylated myosin light chain(MLC)and phosphorylated MLC in ASMCs were analyzed using Western blotting.Results Treatment with rS100A11 attenuated AHR in the rats.ASM contraction assays showed that rS100A11 reduced the contractile responses of isolated tracheal rings and primary ASMCs treated with ACh.In addition,rS100A11 markedly decreased the ACh-induced phosphorylation of the myosin light chain in ASMCs.Moreover,rS100A11 also suppressed the contractile response of tracheal rings in calcium-free buffer medium.Conclusion These results indicate that S100A11 protein can relieve AHR by relaxing ASM independently of extracellular calcium.Our data support the idea that S100A11 is a potential therapeutic target for reducing airway resistance in asthma patients.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.81973952 and No.81774429)the Natural Science Foundation of Shanghai(No.19ZR1451500),and the Yangfan Innovation Project(No.20YF1445300).
文摘Objective S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities.We previously reported that S100A11 was differentially expressed in the respiratory tracts of asthmatic rats as compared with normal controls.Here,we aimed to analyze the potential of S100A11 to regulate both allergen-induced airway hyperresponsiveness(AHR)as well as acetylcholine(ACh)-induced hypercontractility of airway smooth muscle(ASM)and contraction of ASM cells(ASMCs).Methods Purified recombinant rat S100A11 protein(rS100A11)was administered to OVA-sensitized and challenged rats and then the AHR of animals was measured.The relaxation effects of rS100A11 on ASM were detected using isolated tracheal rings and primary ASMCs.The expression levels of un-phosphorylated myosin light chain(MLC)and phosphorylated MLC in ASMCs were analyzed using Western blotting.Results Treatment with rS100A11 attenuated AHR in the rats.ASM contraction assays showed that rS100A11 reduced the contractile responses of isolated tracheal rings and primary ASMCs treated with ACh.In addition,rS100A11 markedly decreased the ACh-induced phosphorylation of the myosin light chain in ASMCs.Moreover,rS100A11 also suppressed the contractile response of tracheal rings in calcium-free buffer medium.Conclusion These results indicate that S100A11 protein can relieve AHR by relaxing ASM independently of extracellular calcium.Our data support the idea that S100A11 is a potential therapeutic target for reducing airway resistance in asthma patients.
