Upregulation of Mas-related G Protein coupled receptor X2 in asthmatic lung mast cells and its activation by the novel neuropeptide hemokinin-1

Respiratory Research

Chizobam Idahosa¹  Hydar Ali²  Saptarshi Roy²  Wichayapha Manorak²  Kshitij Gupta²  Reynold Panettieri³ 

[1] Department of Oral Medicine, School of Dental Medicine;Department of Pathology, School of Dental Medicine, University of Pennsylvania;Rutgers Institute for Translational Medicine and Science, Rutgers University;

关键词: Hemokinin-1;    Substance P;    Lung mast cells;    MRGPRX2;    NK-1R;    Asthma;   

DOI  :  10.1186/s12931-017-0698-3

来源: DOAJ

【 摘 要 】

Abstract Hemokinin-1 (HK-1) is a novel neuropeptide produced by human bronchial cells and macrophages and causes contraction of human bronchi ex vivo. It is also generated by antigen/IgE-activated murine mast cells (MCs) and contributes to experimental chronic allergic airway inflammation via the activation of the neurokinin receptor-1 (NK-1R) expressed on murine MCs. We found elevated MC numbers in the lungs of individuals who died from asthma (asthma) when compared to lungs of individuals who died from other causes (non-asthma). Mas-related G Protein coupled receptor X2 (MRGPRX2) is a novel G-protein coupled receptor (GPCR) that is expressed predominantly on human MCs. We detected low level of MRGPRX2 in non-asthma lung MCs but its expression was significantly upregulated in asthma lung MCs. HK-1 caused degranulation in a human MC line (LAD2) and RBL-2H3 cells stably expressing MRGPRX2 and this response was resistant to inhibition by an NK-1R antagonist. However, knockdown of MRGPRX2 in LAD2 cells resulted in substantial inhibition of HK-1-induced degranulation. These findings suggest that while HK-1 contributes to the development of experimental asthma in mice via NK-1R on murine MCs the effect of this neuropeptide on human bronchoconstriction likely reflects the activation of MRGPRX2 on lung MCs. Thus, development of selective MRGPRX2 antagonists could serve as novel target for the modulation of asthma.

【 授权许可】

Unknown