Low-grade inflammation causes gap junction-coupled cell dysfunction throughout the body, which can lead to the spread of systemic inflammation

Abstract

Background and aims Gap junction-coupled cells form networks in different organs in the body. These networks can be affected by inflammatory stimuli and become dysregulated. Cell signaling is also changed through connexin-linked gap junctions. This alteration affects the surrounding cells and extracellular matrix in organs. These changes can cause the spread of inflammatory substances, thus affecting other network-linked cells in other organs in the body, which can give rise to systemic inflammation, which in turn can lead to pain that can turn into chronic. Methods This is a review based on literature search and our own research data of inflammatory stimuli that can affect different organs and particularly gap-junction-coupled cells throughout the body. Conclusions A remaining question is which cell type or tissue is first affected by inflammatory stimuli. Can endotoxin exposure through the air, water and body start the process and are mast cells the first target cells that have the capacity to alter the physiological status of gap junction-coupled cells, thereby causing breakdown of different barrier systems? Implications Is it possible to address the right cellular and biochemical parameters and restore inflammatory systems to a normal physiological level by therapeutic strategies?

Anti-inflammatory effects induced by ultralow concentrations of bupivacaine in combination with ultralow concentrations of sildenafil (Viagra) and vitamin D3 on inflammatory reactive brain astrocytes

“…Gap junction-coupled cell networks can be targets when the body or different organs are exposed to inflammatory stimuli, such as bacteria or viruses [1,2]. Astrocytes in the central nervous system (CNS) have been studied for several decades regarding their physiological and network coupling properties.…”

Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat

“…Activated astrocytes can promote pain due to release of proinflammatory cytokines [16]. Astrocytes may promote pain also by forming gap junctions between astrocytes and neurons as well as surrounding astrocytes [18]. These gap junctions can be decoupled with carbenoxolone, which results in reduced pain hypersensitivity following, e.g., sleep deprivation [14] or nerve injury [19].…”

Dibenzocyclooctadiene Lignans from Schisandra chinensis with Anti-Inflammatory Effects

“…Gap junction-coupled cells can be found in various organs in the body, where GJIC helps to maintain tissue homeostasis and protects the cells from harmful substances and conditions such as oxidative stress or inflammation [ 24 ]. Disruption and dysregulation of communication by inflammatory mediators or endotoxins (lipopolysaccharides-LPS) can cause inflammatory substances to spread to other cells and organs in the body and can lead to systemic inflammation [ 25 ]. Furthermore, disruption of GJIC can be a factor promoting cancerogenesis.…”