Editing Inflammation (section)

=== Resolution ===
The inflammatory response must be actively terminated when no longer needed to prevent unnecessary "bystander" damage to tissues.<ref name="robspath" /> Failure to do so results in chronic inflammation, and cellular destruction. Resolution of inflammation occurs by different mechanisms in different tissues.
Mechanisms that serve to terminate inflammation include:<ref name="robspath" /><ref>{{Cite journal |vauthors=Eming SA, Krieg T, Davidson JM |date=March 2007 |title=Inflammation in wound repair: molecular and cellular mechanisms |journal=The Journal of Investigative Dermatology |volume=127 |issue=3 |pages=514–25 |doi=10.1038/sj.jid.5700701 |pmid=17299434 |doi-access=free}}</ref>

{{columns-list|colwidth=30em|
* Short [[half-life]] of [[inflammatory mediators]] ''in vivo''.
* Production and release of [[transforming growth factor (TGF) beta]] from [[macrophages]]<ref>{{Cite journal |vauthors=Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, Mizel DE, Anzano M, Greenwell-Wild T, Wahl SM, Deng C, Roberts AB |date=September 1999 |title=Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response |journal=Nature Cell Biology |volume=1 |issue=5 |pages=260–6 |doi=10.1038/12971 |pmid=10559937 |s2cid=37216623}}</ref><ref>{{Cite journal |vauthors=Ashcroft GS |date=December 1999 |title=Bidirectional regulation of macrophage function by TGF-beta |url=https://zenodo.org/record/1260212 |url-status=live |journal=Microbes and Infection |volume=1 |issue=15 |pages=1275–82 |doi=10.1016/S1286-4579(99)00257-9 |pmid=10611755 |archive-url=https://web.archive.org/web/20200110215702/https://zenodo.org/record/1260212 |archive-date=10 January 2020 |access-date=11 September 2019}}</ref><ref>{{Cite journal |vauthors=Werner F, Jain MK, Feinberg MW, Sibinga NE, Pellacani A, Wiesel P, Chin MT, Topper JN, Perrella MA, Lee ME |date=November 2000 |title=Transforming growth factor-beta 1 inhibition of macrophage activation is mediated via Smad3 |journal=The Journal of Biological Chemistry |volume=275 |issue=47 |pages=36653–8 |doi=10.1074/jbc.M004536200 |pmid=10973958 |doi-access=free}}</ref>
* Production and release of [[interleukin 10]] (IL-10)<ref>{{Cite journal |vauthors=Sato Y, Ohshima T, Kondo T |date=November 1999 |title=Regulatory role of endogenous interleukin-10 in cutaneous inflammatory response of murine wound healing |journal=Biochemical and Biophysical Research Communications |volume=265 |issue=1 |pages=194–9 |doi=10.1006/bbrc.1999.1455 |pmid=10548513}}</ref>
* Production of anti-inflammatory [[specialized proresolving mediators]], i.e. [[lipoxin]]s, [[resolvin]]s, [[maresin]]s, and [[neuroprotectin]]s<ref>{{Cite journal |vauthors=Serhan CN |date=August 2008 |title=Controlling the resolution of acute inflammation: a new genus of dual anti-inflammatory and proresolving mediators |journal=Journal of Periodontology |volume=79 |issue=8 Suppl |pages=1520–6 |doi=10.1902/jop.2008.080231 |pmid=18673006}}</ref><ref name="pmid25911383">{{Cite journal |vauthors=Headland SE, Norling LV |date=May 2015 |title=The resolution of inflammation: Principles and challenges |journal=Seminars in Immunology |volume=27 |issue=3 |pages=149–60 |doi=10.1016/j.smim.2015.03.014 |pmid=25911383}}</ref>
* Downregulation of pro-inflammatory molecules, such as [[leukotrienes]].
* Upregulation of anti-inflammatory molecules such as the [[interleukin 1 receptor antagonist]] or the soluble [[tumor necrosis factor receptor]] (TNFR)
* [[Apoptosis]] of pro-inflammatory cells<ref>{{Cite journal |vauthors=Greenhalgh DG |date=September 1998 |title=The role of apoptosis in wound healing |journal=The International Journal of Biochemistry & Cell Biology |volume=30 |issue=9 |pages=1019–30 |doi=10.1016/S1357-2725(98)00058-2 |pmid=9785465}}</ref>
* Desensitization of receptors.
* Increased survival of cells in regions of inflammation due to their interaction with the [[extracellular matrix]] (ECM)<ref>{{Cite journal |vauthors=Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, Prestwich GD, Mascarenhas MM, Garg HG, Quinn DA, Homer RJ, Goldstein DR, Bucala R, Lee PJ, Medzhitov R, Noble PW |date=November 2005 |title=Regulation of lung injury and repair by Toll-like receptors and hyaluronan |journal=Nature Medicine |volume=11 |issue=11 |pages=1173–9 |doi=10.1038/nm1315 |pmid=16244651 |s2cid=11765495}}</ref><ref>{{Cite journal |vauthors=Teder P, Vandivier RW, Jiang D, Liang J, Cohn L, Puré E, Henson PM, Noble PW |date=April 2002 |title=Resolution of lung inflammation by CD44 |journal=Science |volume=296 |issue=5565 |pages=155–8 |bibcode=2002Sci...296..155T |doi=10.1126/science.1069659 |pmid=11935029 |s2cid=7905603}}</ref>
* Downregulation of receptor activity by high concentrations of [[ligands]]
* Cleavage of [[chemokine]]s by [[matrix metalloproteinases]] (MMPs) might lead to production of anti-inflammatory factors.<ref>{{Cite journal |vauthors=McQuibban GA, Gong JH, Tam EM, McCulloch CA, Clark-Lewis I, Overall CM |date=August 2000 |title=Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3 |journal=Science |volume=289 |issue=5482 |pages=1202–6 |bibcode=2000Sci...289.1202M |doi=10.1126/science.289.5482.1202 |pmid=10947989}}</ref>
}}
{{Cquote|Acute inflammation normally resolves by mechanisms that have remained somewhat elusive. Emerging evidence now suggests that an active, coordinated program of resolution initiates in the first few hours after an inflammatory response begins. After entering tissues, [[granulocyte]]s promote the switch of [[arachidonic acid]]–derived [[prostaglandin]]s and [[leukotriene]]s to lipoxins, which initiate the termination sequence. [[Neutrophil]] recruitment thus ceases and programmed death by [[apoptosis]] is engaged. These events coincide with the biosynthesis, from [[omega-3 fatty acid|omega-3 polyunsaturated fatty acids]], of [[resolvins]] and [[Neuroprotectin|protectins]], which critically shorten the period of neutrophil infiltration by initiating apoptosis. As a consequence, apoptotic neutrophils undergo [[phagocytosis]] by [[macrophage]]s, leading to neutrophil clearance and release of anti-inflammatory and reparative [[cytokines]] such as transforming growth factor-β1. The anti-inflammatory program ends with the departure of macrophages through the [[Lymphatic system|lymphatics]].<ref name="pmid16369558">{{Cite journal |vauthors=Serhan CN, Savill J |date=December 2005 |title=Resolution of inflammation: the beginning programs the end |journal=Nature Immunology |volume=6 |issue=12 |pages=1191–7 |doi=10.1038/ni1276 |pmid=16369558 |s2cid=22379843}}</ref>|30px|30px|[[Charles N. Serhan]]
}}