Resolution of Inflammation: What Controls Its Onset?

Abstract

An effective resolution program may be able to prevent the progression from non-resolving acute inflammation to persistent chronic inflammation. It has now become evident that coordinated resolution programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide the fine-tuning of inflammation and create a favorable environment for the resolution phase to take place and for homeostasis to return. In this review, we focus on the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution. We suggest that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution. Indeed, several events enact a decrease in the local chemokine concentration, a reduction which is essential to inhibit further infiltration of neutrophils into the tissue. Interestingly, although neutrophils are cells that characteristically participate in the active phase of inflammation, they also contribute to the onset of resolution. Further understanding of the molecular mechanisms that initiate resolution may be instrumental to develop pro-resolution strategies to treat complex chronic inflammatory diseases, in humans. The efforts to develop strategies based on resolution of inflammation have shaped a new area of pharmacology referred to as “resolution pharmacology.”

Resolving Lipid Mediators Maresin 1 and Resolvin D2 Prevent Atheroprogression in Mice

“…35 These observations then suggest a positive feedback loop, by the administration of MaR1 and RvD2, that further feeds resolution of inflammation and halts atheroprogression. Indeed, positive loops of resolution have been previously reported, 47 such as the stimulation of synthesis of Lipoxin A4 by Resolvin E1. 48 MaR1-and RvD2-treated mice exhibited lesions with increased levels of collagen, when compared with vehicle-treated group.…”

“…Moreover, proresolution mediators have been associated with positive feedback loops, where one proresolving mediator induces another. 47 On the contrary, anti-inflammatory drugs, such as those inhibiting COX-2 (cyclooxygenase 2), have been reported to delay the resolution of inflammation, by disrupting the production of anti-inflammatory prostaglandins and lipoxins. [51][52][53][54] Thus, our study is in support of the potential translational relevance of resolution-inducing agonists in cardiovascular disease progression.…”

Mesenchymal stem cells-derived exosomal microRNAs contribute to wound inflammation

“…Immune cells, mainly resident macrophages, dendritic cells, and neutrophils, are activated during inflammation and recruited to the impaired site to initiate the healing process by eradicating pathogens and damaged cells. Although an acute and well-regulated inflammatory response is typically crucial for returning cells and organisms to homeostasis, chronic and inappropriate inflammation is hazardous to tissues and predisposes patients to the *Corresponding author (email: fuxiaobing@vip.sina.com) **Corresponding author (email: hanwdrsw69@yahoo.com) onset or progression of delayed wound healing (Sugimoto et al, 2016;Landén et al, 2016). Therefore, the regulation of inflammation is a potential therapeutic target for intervention to reduce the risk of disease and disability.…”

“…It has been reported that several miRNAs play crucial roles in regulating different inflammatory responses in many tissues and affect the phenotype and development of immune cells. Dysregulation of miR-21 or miR-181 induces a chronic inflammatory state; this miRNA is key in controlling the balance between initial pro-inflammatory and later immuno-regulatory, anti-inflammatory responses (Garo and Murugaiyan, 2016;Sun et al, 2014). As master molecular switches, miRNAs exchange bio-information between neighboring cells and are important in exosome-mediated microenvironmental changes (Cavalieri et al, 2016;Navakanitworakul et al, 2016).…”

Osteoarthritis: Current Clinical Concept and Some Promising Therapeutic Approaches

“…Разре-шение воспаления, таким образом, представляется актив-ным процессом. Оно успешно происходит в случае прекра-щения повреждения живой ткани: концентрация DAMP снижается, синтез цитокинов и медиаторов воспаления прекращается (в этом процессе важнейшее значение имеет нарастание синтеза RvE 1-3 и RvD 1-3 ), а уже синтезирован-ные субстанции подвергаются биодеградации; клетки «воспалительного ответа» теряют жизнеспособность, раз-рушаются и фагоцитируются М2-макрофагами [20][21][22].…”