Editorial The Role of Lipids Mediators in Inflammation and...
Transcript of Editorial The Role of Lipids Mediators in Inflammation and...
EditorialThe Role of Lipids Mediators in Inflammation and Resolution
Alexandre de Paula Rogerio,1 Carlos Artério Sorgi,2 Ruxana Sadikot,3 and Troy Carlo4
1Departamento de Clınica Medica, Laboratorio de Imunofarmacologia Experimental (LIFE), Instituto de Ciencias da Saude,Universidade Federal do Triangulo Mineiro (UFTM), Rua Vigario Carlos 162, 38025-350 Uberaba, MG, Brazil2Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, 14049-903 Sao Paulo, SP, Brazil3Pulmonary, Critical Care, Sleep and Allergy Medicine, University of Florida, Gainesville, FL 32610, USA4Pulmonary and Critical Care Medicine Division, Brigham and Women’s Hospital, Boston, MA 02115, USA
Correspondence should be addressed to Alexandre de Paula Rogerio; [email protected]
Received 8 December 2014; Accepted 8 December 2014
Copyright © 2015 Alexandre de Paula Rogerio et al. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.
Acute inflammation is generally self-limited. However, ifacute inflammation fails to resolve, chronic inflammation canpersist. The innate and adaptive immune systems, as well asstructural cells, modulate the length and intensity of inflam-matory responses. Aberrant immune responses, includingthose induced by allergens, environmental pollutants, infec-tious agents, acids, and other noxious stimuli, promoteexcessive leukocyte recruitment and the production of proin-flammatory cytokines, lipids mediators, and chemokines,which are critical to initiate and maintain the inflamma-tory process. Lipids mediators, derived from the omega-6polyunsaturated fatty acids (PUFA) including leukotrienes(LTs) and prostaglandins (PGs), are potent enhancers ofinnate and adaptive immune activity and are implicated innumerous inflammatory disorders. Yet certain PGs, suchas PGD
2and PGE
2, demonstrate anti-inflammatory effects.
Similarly, lipoxins (LXs), derived from the omega-6 PUFAarachidonic acid, not only harbor potent anti-inflammatoryactivity, but also promote the resolution of inflammation.Complete resolution of inflammatory responses is criticalfor human health. Resolution is an active process that isregulated, in part, by specialized proresolving mediatorssuch as the omega-3 PUFA derived resolvins, maresins, andprotectins, in addition to the aforementioned LXs. Thesebiochemical mediators signal through distinct receptors toboth dampen inflammation and promote resolution.
This special issue covers the most recent researchelucidating the role of these lipids mediators in inflammationand the resolution of inflammation.
In recent decades, considerable progress has been madein understanding the role of lipoxin A
4in health and disease.
Two elegant reviews by Higgins et al. and Martini et al.illustrate the critical role LXA
4plays in patients with cystic
fibrosis and neurological diseases, respectively.Cystic fibrosis, an autosomal disease, leads to, among
others, devastating infection and inflammation of the air-ways. Patients suffering from cystic fibrosis display decreasedLXA4production when compared to healthy individuals
suggesting that this decrement contributes to continuouslocal inflammation. Interestingly, LXA
4triggers responses
in bronchial epithelial cells that would be beneficial to CFpatients. Exposure to LXA
4stimulates a rapid and transient
intracellular Ca2+ increase and whole-cell Cl− currents thatrestore fluid transport in cystic fibrosis, increases the airwaysurface liquid height via P2Y11 activation, and enhancesepithelial cell migration and proliferation, activities crucial tothe repair of epithelia. Thus, LXA
4demonstrates therapeutic
potential for patients with cystic fibrosis.Neurological diseases and conditions, such as
Alzheimer’s, Parkinson’s, traumatic brain injury, and strokeas well as conditions leading to chronic neuropathic pain,typically present marked transient or continued neuroin-flammation. Interestingly, Alzheimer’s patients are slowto resolve inflammation and display lower LXA
4levels in
cerebrospinal fluid and hippocampus samples comparedto control subjects. Aspirin-triggered 15-epi-lipoxin A
4
promoted decreased inflammation in a murine model ofAlzheimer’s by reducing proinflammatory and increasing
Hindawi Publishing CorporationBioMed Research InternationalVolume 2015, Article ID 605959, 2 pageshttp://dx.doi.org/10.1155/2015/605959
2 BioMed Research International
anti-inflammatory mediators in the brain. Taken together,these demonstrate the neuroprotective properties of LXA
4.
Protozoan infections cause serious health, political,social, and economic problems. In an experimental model,Sacramento et al. demonstrated that 5-lipoxygenase knock-out animals displayed increased susceptibility to infectionwith Leishmania infantum as measured by an increase inparasitic load in several organs as well as decreased neu-trophil migration to the infectious foci. In addition to theseeffects, reductions in proinflammatory cytokines involvedin T cell differentiation to Th17 axis were observed. Theseresults demonstrated that LTs play an important role in thecontrolling of L. infantum-induced visceral leishmaniasis.
Cysteinyl leukotrienes (cysLTs), like LTs, play an impor-tant role in diseases, such as asthma.Allergic asthma is a com-plex inflammatory disorder characterized by airway hyper-responsiveness, eosinophilic inflammation, hypersecretion ofmucus, and tissue remodeling. The asthma pathophysiologyinvolves chemical mediators that play an important role inthe establishment of inflammation. Baptista-dos-Reis et al.review the roles of cysLTs in eliciting eosinophil granuleprotein secretion and emphasize the importance of thisfinding in eosinophil immunobiology and in eosinophilicdiseases.
Allergen exposure may induce changes in brainstemsecondary neurons, with neural sensitization of the nucleussolitary tract, which can be considered one of the causes ofthe airway hyperresponsiveness, a characteristic feature ofasthma. Based on these considerations, Spaziano et al. eval-uated functional, morphological, and biochemical changesoccurring in the nucleus solitary tract following airwaysensory nerve activation in naive and ovalbumin sensitizedrats.
The role of inflammation in diabetes is widely known.Tessaro et al. carefully review the roles eicosanoids play indiabetes-related nephropathy, retinopathy, and cardiovascu-lar events.
Acknowledgment
We would like to thank the authors across the world fortheir valuable contributions to this special issue as wellas the reviewers for their constructive comments to themanuscripts. We encourage and appreciate your furthersupport for this annual/special issue series.
Alexandre de Paula RogerioCarlos Arterio Sorgi
Ruxana SadikotTroy Carlo
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