Modulation of the inflammatory response to chitosan through M2 macrophage polarization using pro-resolution mediators

Vasconcelos, Daniela P.; Costa, María Teresa; Amaral, Isabel F.; Barbosa, Mário A.; Águas, Artur P.; Barbosa, Judite N.

doi:10.1016/j.biomaterials.2014.10.035

Cited by 136 publications

(90 citation statements)

References 26 publications

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“…The LXA 4 -induced shift in WAT MΦ phenotype correlated with other attributes of resolution, such as attenuation of the inflammatory cytokine TNF-α. These data may be compared with other in vivo models, where LXA 4 promotes an M1- to-M2 MΦ polarization in a mouse air-pouch model of inflammation (Vasconcelos et al, 2015). Indeed, LXA 4 may attenuate the pro-inflammatory M1 MΦ phenotype by modulating IκBα degradation, NF-κB translocation and IKK expression, resulting in supressed NF-κB activation (Huang et al, 2014; Kure et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease

et al. 2015

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SUMMARY The role of inflammation in obesity-related pathologies is well established. We investigated the therapeutic potential of LipoxinA4 (LXA4:5(S),6(R),15(S)-trihydroxy-7E,9E,11Z,13E,-eicosatetraenoic acid) and a synthetic 15(R)-Benzo-LXA4-analogue, as interventions in a 3-month high-fat-diet [HFD; 60%fat]-induced obesity model. Obesity caused distinct pathologies, including impaired glucose-tolerance, adipose inflammation, fatty liver and chronic-kidney-disease (CKD). Lipoxins (LXs) attenuated obesity- induced CKD; reducing glomerular expansion, mesangial matrix and urinary H2O2. Furthermore, LXA4 reduced liver weight, serum alanine-aminotransferase and hepatic triglycerides. LXA4 decreased obesity-induced adipose inflammation, attenuating TNF-α and CD11c+ M1-macrophages (MΦs), while restoring CD206+ M2-MΦs and increasing Annexin-1. LXs did not affect renal or hepatic MΦs, suggesting protection occurred via attenuation of adipose inflammation. LXs restored adipose expression of autophagy markers LC3-II and p62. LX-mediated protection was demonstrable in adiponectin−/− mice, suggesting that the mechanism was adiponectin independent. In conclusion, LXs protect against obesity- induced systemic disease and these data support a novel therapeutic paradigm for treating obesity and associated pathologies.

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Section: Discussionmentioning

confidence: 99%

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease

et al. 2015

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“…M2a (alternative activation) subpopulations respond to IL‐4 and IL‐13 and are associated with parasitic defense and Th2 cell response; M2b (type II alternative activation) cells are stimulated with IL‐1 and ligation of CD16, CD32, and CD64 and are associated with immunoregulation; M2c (acquired deactivation) subpopulations are stimulated via IL‐10 and glucocorticoids, have increased expression of TGFβ and CD163, and are important in tissue remodeling and immunoregulation (Martinez & Gordon, 2014; Walker & Lue, 2015). LXA 4 has been shown to induce phagocytosis and debris clearance in macrophages, an important characteristic of M2 cells (Godson et al., 2000; Vasconcelos et al., 2015). Here, we report for the first time that 1 week of BML‐111 treatment increases CD163 + microglia/macrophage cell populations in the brain 1 week post‐stroke, indicating that BML‐111 may increase the M2c subpopulation as a mechanism of action to promote debris clearance and tissue remodeling.…”

Section: Discussionmentioning

confidence: 99%

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

et al. 2017

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BackgroundResolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA 4) is an anti‐inflammatory, pro‐resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA 4 is rapidly inactivated, potent analogs have been synthesized, including BML‐111. We hypothesized that post‐ischemic, intravenous treatment with BML‐111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats. Additionally, we investigated the potential protective mechanisms of BML‐111 on the post‐stroke molecular and cellular profile.MethodsA total of 133 male Sprague‐Dawley rats were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) and BML‐111 administration was started at the time of reperfusion. Two methods of week‐long BML‐111 intravenous administration were tested: continuous infusion via ALZET ® osmotic pumps (1.25 and 3.75 μg μl−1 hr−1), or freshly prepared daily single injections (0.3, 1, and 3 mg/kg). We report for the first time on the stability of BML‐111 and characterized an optimal dose and a dosing schedule for the administration of BML‐111.ResultsOne week of BML‐111 intravenous injections did not reduce infarct size or improve behavioral deficits 4 weeks after ischemic stroke. However, post‐ischemic treatment with BML‐111 did elicit early protective effects as demonstrated by a significant reduction in infarct volume and improved sensorimotor function at 1 week after stroke. This protection was associated with reduced pro‐inflammatory cytokine and chemokine levels, decreased M1 CD40+ macrophages, and increased alternatively activated, anti‐inflammatory M2 microglia/macrophage cell populations in the post‐ischemic brain.ConclusionThese data suggest that targeting the endogenous LXA 4 pathway could be a promising therapeutic strategy for the treatment of ischemic stroke. More work is necessary to determine whether a different dosing regimen or more stable LXA 4 analogs could confer long‐term protection.

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“…They demonstrated that both molecules shifted the M1 macrophage inflammatory response to an M2 reparative response and decreased several pro-inflammatory cytokines. Recently, the same group developed chitosan-based 3D porous scaffolds loaded with RvD1 by dispersing RvD1 over freeze-dried scaffolds followed by a second freeze-drying step [69]. The authors investigated the inflammatory response caused by this biomaterial in an in vivo model (the mouse air-pouch model of inflammation) and found a significant shift towards an M2 macrophage population and a decrease in the inflammatory cells around and within the implanted scaffolds.…”

Section: Delivering Molecules To Control Macrophage Polarizationmentioning

confidence: 99%

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

Álvarez

Liu

Santiago

et al. 2016

Journal of Controlled Release

200

119

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Macrophages are key players in many physiological scenarios including tissue homeostasis. In response to injury, typically the balance between macrophage sub-populations shifts from an M1 phenotype (pro-inflammatory) to an M2 phenotype (anti-inflammatory). In tissue engineering scenarios, after implantation of any device, it is desirable to exercise control on this M1-M2 progression and to ensure a timely and smooth transition from the inflammatory to the healing stage. In this review, we briefly introduce the current state of knowledge regarding macrophage function and nomenclature. Next, we discuss the use of controlled release strategies to tune the balance between the M1 and M2 phenotypes in the context of tissue engineering applications. We discuss recent literature related to the release of anti-inflammatory molecules (including nucleic acids) and the sequential release of cytokines to promote a timely M1-M2 shift. In addition, we describe the use of macrophages as controlled release agents upon stimulation by physical and/or mechanical cues provided by scaffolds. Moreover, we discuss current and future applications of “smart” implantable scaffolds capable of controlling the cascade of biochemical events related to healing and vascularization. Finally, we provide our opinion on the current challenges and the future research directions to improve our understanding of the M1-M2 macrophage balance and properly exploit it in tissue engineering and regenerative medicine applications.

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Modulation of the inflammatory response to chitosan through M2 macrophage polarization using pro-resolution mediators

Cited by 136 publications

References 26 publications

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

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Modulation of the inflammatory response to chitosan through M2 macrophage polarization using pro-resolution mediators

Cited by 136 publications

References 26 publications

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A4 analog: Protective mechanisms and long‐term effects on neurological recovery

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

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Product

Resources

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Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery