title: Inflammasome biology in fibrogenesis.
abstract: Pathogens and sterile insults both result in an inflammatory response. A significant part of this response is mediated by cytosolic machinery termed as the inflammasome which results in the activation and secretion of the cytokines interleukin-1β (IL-1β) and IL-18. Both of these are known to result in the activation of an acute inflammatory response, resulting in the production of downstream inflammatory cytokines such as tumor necrosis factor (TNF-α), interferon-gamma (IFN-γ), chemotaxis of immune cells, and induction of tissue injury. Surprisingly this very acute inflammatory pathway is also vital for the development of a full fibrogenic response in a number of organs including the lung, liver, and skin. There is evidence for the inflammasome having a direct role on tissue specific matrix producing cells such as the liver stellate cell, and also indirectly through the activation of resident tissue macrophage populations. The inflammasome requires stimulation of two pathways for full activation, and initiating stimuli include Toll-like receptor (TLR) agonists, adenosine triphosphate (ATP), particulates, and oxidative stress. Such a role for an acute inflammatory pathway in fibrosis runs counter to the prevailing association of TGF-β driven anti-inflammatory and pro-fibrotic pathways. This identifies new therapeutic targets which have the potential to simultaneously decrease inflammation, tissue injury and fibrosis. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.
authors.affiliation: Section of Digestive Diseases, Yale University, New Haven, CT, USA; West Haven Veterans Medical Center, New Haven, CT, USA.
authors.forename: Xinshou
authors.initials: X
authors.lastname: Ouyang
authors.forename: Ayaz
authors.initials: A
authors.lastname: Ghani
authors.forename: Wajahat Z
authors.initials: WZ
authors.lastname: Mehal
mesh_terms: D016207:Cytokines / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D053583:Interleukin-1beta; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha