title: MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity: a new perspective for the treatment.
abstract: Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, and bacterial and viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these risk factors lead to the development of AHR is limited. Activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) and their related signal pathways including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and protein kinase A (PKA) signaling pathways may result in airway kinin receptor upregulation, which is suggested to play an important role in the development of AHR. Environmental risk factors trigger the production of pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukins (ILs) that activate intracellular MAPK- and NF-κB-dependent inflammatory pathways, which subsequently lead to AHR via kinin receptor upregulation. Blockage of intracellular MAPK/NF-κB signaling prevents kinin B₁ and B₂ receptor expression in the airways, resulting in a decrease in the response to bradykinin (kinin B₂ receptor agonist) and des-Arg⁹-bradykinin (kinin B₁ receptor agonist). This suggests that MAPK- and NF-κB-dependent kinin receptor upregulation can provide a novel option for treatment of AHR in asthmatic as well as in other inflammatory airway diseases.
authors: Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, People's Republic of China.
authors: Yaping
authors: Y
authors: Zhang
authors: Lars-Olaf
authors: LO
authors: Cardell
authors: Lars
authors: L
authors: Edvinsson
authors: Cang-Bao
authors: CB
authors: Xu
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D007705:Kinins / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000276:immunology*; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D015854:Up-Regulation; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D018836:Inflammation Mediators; D007705:Kinins; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D000097782:NF-kappaB-Inducing Kinase