A review of the pathophysiology and the role of ion channels on bronchial asthma

Abstract

Asthma is one of the main non-communicable chronic diseases and affects a huge portion of the population. It is a multifactorial disease, classified into several phenotypes, being the allergic the most frequent. The pathophysiological mechanism of asthma involves a Th2-type immune response, with high concentrations of allergen-specific immunoglobulin E, eosinophilia, hyperreactivity and airway remodeling. These mechanisms are orchestrated by intracellular signaling from effector cells, such as lymphocytes and eosinophils. Ion channels play a fundamental role in maintaining the inflammatory response on asthma. In particular, transient receptor potential (TRP), stock-operated Ca2+ channels (SOCs), Ca2+-activated K+ channels (IKCa and BKCa), calcium-activated chloride channel (TMEM16A), cystic fibrosis transmembrane conductance regulator (CFTR), piezo-type mechanosensitive ion channel component 1 (PIEZO1) and purinergic P2X receptor (P2X). The recognition of the participation of these channels in the pathological process of asthma is important, as they become pharmacological targets for the discovery of new drugs and/or pharmacological tools that effectively help the pharmacotherapeutic follow-up of this disease, as well as the more specific mechanisms involved in worsening asthma.

ORAI Ca2+ Channels in Cancers and Therapeutic Interventions

“…Dysfunction of CRAC channels can contribute to a myriad of diseases, including bronchial asthma [87,88], airway hyperreactivity [89], cardiovascular diseases [90][91][92], hypocalcemia [93], brain diseases [94][95][96], gastroenteric inflammation [97], as well as various carcinomas [98][99][100][101][102]. Here, we will focus on the role of ORAI in cancer.…”

Synthetic Biology Meets Ca2+ Release-Activated Ca2+ Channel-Dependent Immunomodulation

“…In addition to the CRAC channels’ role in many immune cell functions, they are also potential drug targets for the treatment of various inflammatory reactions, allergic diseases [ 118 , 119 ], and many cancer types [ 20 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. Several studies have confirmed that the genetic deletion or inhibition of CRAC channels hinders T cell and mast cell functions and diminishes inflammation of autoimmunity, transplant rejection, and asthma [ 119 ].…”

“…In addition to the CRAC channels’ role in many immune cell functions, they are also potential drug targets for the treatment of various inflammatory reactions, allergic diseases [ 118 , 119 ], and many cancer types [ 20 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. Several studies have confirmed that the genetic deletion or inhibition of CRAC channels hinders T cell and mast cell functions and diminishes inflammation of autoimmunity, transplant rejection, and asthma [ 119 ]. Particularly, the development and the progression of several T cell-mediated autoimmune diseases, including inflammatory bowel disease [ 129 ] (IBD), experimental autoimmune encephalomyelitis [ 130 , 131 ] (EAE), graft-versus-host disease [ 132 , 133 ] (GvHD), and psoriasis form skin inflammation [ 134 , 135 , 136 ], have been linked to Orai and STIM proteins.…”