Monocyte chemoattractant protein-1/CC chemokine ligand 2 enhances apoptotic cell removal by macrophages through Rac1 activation

Tanaka, Takeshi; Terada, M; Ariyoshi, Koya; Morimoto, Konosuke

doi:10.1016/j.bbrc.2010.07.141

Cited by 40 publications

(39 citation statements)

References 32 publications

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“…Interestingly, it has been reported that MCP-1 enhances efferocytosis by alveolar macrophages, and that MCP-1 is important for the resolution of inflammation [52]. This is consistent with our observations that macrophage numbers were not reduced by RvD1 and that RvD1 enhances efferocytosis (Figure 7).…”

Section: Discussionsupporting

confidence: 93%

A Novel Anti-Inflammatory and Pro-Resolving Role for Resolvin D1 in Acute Cigarette Smoke-Induced Lung Inflammation

et al. 2013

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IntroductionCigarette smoke is a profound pro-inflammatory stimulus that contributes to acute lung injuries and to chronic lung disease including COPD (emphysema and chronic bronchitis). Until recently, it was assumed that resolution of inflammation was a passive process that occurred once the inflammatory stimulus was removed. It is now recognized that resolution of inflammation is a bioactive process, mediated by specialized lipid mediators, and that normal homeostasis is maintained by a balance between pro-inflammatory and pro-resolving pathways. These novel small lipid mediators, including the resolvins, protectins and maresins, are bioactive products mainly derived from dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFA). We hypothesize that resolvin D1 (RvD1) has potent anti-inflammatory and pro-resolving effects in a model of cigarette smoke-induced lung inflammation.MethodsPrimary human lung fibroblasts, small airway epithelial cells and blood monocytes were treated with IL-1β or cigarette smoke extract in combination with RvD1 in vitro, production of pro-inflammatory mediators was measured. Mice were exposed to dilute mainstream cigarette smoke and treated with RvD1 either concurrently with smoke or after smoking cessation. The effects on lung inflammation and lung macrophage populations were assessed.ResultsRvD1 suppressed production of pro-inflammatory mediators by primary human cells in a dose-dependent manner. Treatment of mice with RvD1 concurrently with cigarette smoke exposure significantly reduced neutrophilic lung inflammation and production of pro-inflammatory cytokines, while upregulating the anti-inflammatory cytokine IL-10. RvD1 promoted differentiation of alternatively activated (M2) macrophages and neutrophil efferocytosis. RvD1 also accelerated the resolution of lung inflammation when given after the final smoke exposure.ConclusionsRvD1 has potent anti-inflammatory and pro-resolving effects in cells and mice exposed to cigarette smoke. Resolvins have strong potential as a novel therapeutic approach to resolve lung injury caused by smoke and pulmonary toxicants.

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Section: Discussionsupporting

confidence: 93%

A Novel Anti-Inflammatory and Pro-Resolving Role for Resolvin D1 in Acute Cigarette Smoke-Induced Lung Inflammation

et al. 2013

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“…The engulfment of apoptotic cells relies on the signaling of Rho family GTPases, specifically Rac1, and subsequent cytoskeletal reorganization 31, 32, 33. Consistent with the increase in the number of apoptotic cells engulfed by macrophages (Fig.…”

Section: Resultssupporting

confidence: 66%

Inhibition of Sprouty2 polarizes macrophages toward an M2 phenotype by stimulation with interferon γ andPorphyromonas gingivalislipopolysaccharide

Atomura

Sanui

Fukuda

et al. 2016

Immunity, Inflammation and Disease

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Periodontitis is a chronic inflammatory disorder caused by specific bacteria residing in the biofilm, particularly Porphyromonas gingivalis (Pg). Sprouty2 (Spry2) functions as a negative regulator of the fibroblast growth factor (FGF) signaling pathway. We previously demonstrated that sequestration of Spry2 induced proliferation and osteogenesis in osteoblastic cells by basic FGF (bFGF) and epidermal growth factor (EGF) stimulation in vitro, but diminished cell proliferation in gingival epithelial cells. In addition, Spry2 knockdown in combination with bFGF and EGF stimulation increases periodontal ligament cell proliferation and migration accompanied by prevention of osteoblastic differentiation. In this study, we investigated the mechanisms through which Spry2 depletion by interferon (IFN) γ and Pg lipopolysaccharide (LPS) stimulation affected the physiology of macrophages in vitro. Transfection of macrophages with Spry2 small‐interfering RNA (siRNA) promoted the expression of genes characteristic of M2 alternative activated macrophages, induced interleukin (IL)‐10 expression, and enhanced arginase activity, even in cells stimulated with IFNγ and Pg LPS. In addition, we found that phosphoinositide 3‐kinase (PI3K) and AKT activation by Spry2 downregulation enhanced efferocytosis of apoptotic cells by increasing Rac1 activation and decreasing nuclear factor kappa B (NFκB) p65 phosphorylation but not signal transducer and activator of transcription 1 (STAT1) phosphorylation. Collectively, our results suggested that topical administration of Spry2 inhibitors may efficiently resolve inflammation in periodontal disease as macrophage‐based anti‐inflammatory immunotherapy and may create a suitable environment for periodontal wound healing. These in vitro findings provide a molecular basis for new therapeutic approaches in periodontal tissue regeneration.

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“…It seems that NRF2 induction through RAC1 is KEAP1-independent in our model even though KEAP1 overexpression inhibits RAC1 on the formation of E-cadherin-mediated cell-cell adhesion (37). It has been widely reported that RAC1 participates in several signaling kinase pathways, including MAPKs and PI3K (38,39). Our group has reported a KEAP-independent regulation of NRF2 that relies on signaling kinases PI3K/AKT (40).…”

Section: Discussionmentioning

confidence: 59%

Transcription Factors NRF2 and NF-κB Are Coordinated Effectors of the Rho Family, GTP-binding Protein RAC1 during Inflammation

Cuadrado

Martín‐Moldes

et al. 2014

Journal of Biological Chemistry

267

186

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Background: RAC1 is a small G-protein of the Rho family that activates the transcription factor NF-B to elicit an inflammatory response. Results: We have found that RAC1 also induces the NRF2/ARE pathway, which in term blocks RAC1-dependent NF-B activation. Conclusion: RAC1 modulates inflammation by coordinating the activity of pro-inflammatory NF-B and anti-oxidant NRF2 transcription factors. Significance: Therapeutic intervention on RAC1 could help modulate pro-and anti-inflammatory processes.

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Monocyte chemoattractant protein-1/CC chemokine ligand 2 enhances apoptotic cell removal by macrophages through Rac1 activation

Cited by 40 publications

References 32 publications

A Novel Anti-Inflammatory and Pro-Resolving Role for Resolvin D1 in Acute Cigarette Smoke-Induced Lung Inflammation

A Novel Anti-Inflammatory and Pro-Resolving Role for Resolvin D1 in Acute Cigarette Smoke-Induced Lung Inflammation

Inhibition of Sprouty2 polarizes macrophages toward an M2 phenotype by stimulation with interferon γ andPorphyromonas gingivalislipopolysaccharide

Transcription Factors NRF2 and NF-κB Are Coordinated Effectors of the Rho Family, GTP-binding Protein RAC1 during Inflammation

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