Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease

Abstract

Inflammation occurs as a result of exposure of tissues and organs to harmful stimuli such as microbial pathogens, irritants, or toxic cellular components. The primary physical manifestations of inflammation are redness, swelling, heat, pain, and loss of function to the affected area. These processes involve the major cells of the immune system, including monocytes, macrophages, neutrophils, basophils, dendritic cells, mast cells, T-cells, and B-cells. However, examination of a range of inflammatory lesions demonstrates the presence of specific leukocytes in any given lesion. That is, the inflammatory process is regulated in such a way as to ensure that the appropriate leukocytes are recruited. These events are in turn controlled by a host of extracellular molecular regulators, including members of the cytokine and chemokine families that mediate both immune cell recruitment and complex intracellular signalling control mechanisms that characterise inflammation. This review will focus on the role of the main cytokines, chemokines, and their receptors in the pathophysiology of auto-inflammatory disorders, pro-inflammatory disorders, and neurological disorders involving inflammation.

The exaggerated inflammatory response in Behçet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-γ/CXCL10 IP-10 pathway

“…Chemokines are low molecular weight cytokines primarily responsible for chemotaxis of either specific leucocytes or groups of leucocytes [7]. CXCL10, along with the closely related chemokines CXCL9 and CXCL11, is an interferon (IFN)-g-inducible agonist for the CXCR3 chemokine receptor, which is rapidly induced on naive T cells following activation, and remains highly expressed by Th1 CD4…”

β2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury

“…Cells of the innate immune system including monocytes/macrophages, mast cells, and neutrophils play critical roles in infarct healing through tissue phagocytosis and activation of reparative responses. Recruitment and trafficking of these leukocytes to the heart following acute injury occur through the action of chemokines on their receptors to promote their migration to the site of injury (2), and have been the focus of much research in recent years (1,3).…”

Talking to the Brain at the Blood-Brain Barrier through Inflammation-Induced Prostaglandin E2

“…Since then, researchers have identified more than 300 cytokines (ILs, IFNs, TNFs, growth factors and chemokines) (Turner et al, 2014). These extracellular molecules are primarily produced to support the functions of the immune cells, and trafficking and communication between them, but also with and between somatic cells (from Greek, cyto-, cell and -kinos, movement), in health as well as during pathological processes.…”

“…It is well-known that low doses of IL-1β are enough to induce specific responses. On a cellular level, it was shown that as few as 2% of all IL-1R1 need to be activated to induce an effect (Arend, 2002;Dinarello et al, 2012;Garlanda et al, 2013;Sims and Smith, 2010;Turner et al, 2014).…”

“…Today the TNF superfamily includes 30 receptors and 19 associated ligands [reviewed in (Aggarwal, 2003;Tracey et al, 2008;Turner et al, 2014)]. TNFα plays important roles in cell differentiation, inflammation, immunity, metabolism and apoptosis.…”