The Oxidative Stress Product Carboxyethylpyrrole Potentiates TLR2/TLR1 Inflammatory Signaling in Macrophages

Saeed, Ali; Duffort, Stéphanie; Ivanov, Dmitry; Wang, Hua; Laird, James; Salomon, Robert G.; Cruz-Guilloty, Fernando; Pérez, Víctor L.

doi:10.1371/journal.pone.0106421

Cited by 27 publications

(31 citation statements)

References 58 publications

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“…However, subsequent reports have questioned the priming ability of CEPadducted proteins and rather found it to potentiate inflammasome priming by other signals (35). In our experiments, we did not observe a priming effect of HNE-adducted POS in RPE cells.…”

Section: Discussioncontrasting

confidence: 81%

Complement Component C5a Primes Retinal Pigment Epithelial Cells for Inflammasome Activation by Lipofuscin-mediated Photooxidative Damage

Brandstetter

Holz

Krohne

2015

Journal of Biological Chemistry

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Background: Complement activation and oxidative damage contribute to retinal pigment epithelium (RPE) pathology in age-related macular degeneration (AMD). Results: C5a induces interleukin-1␤ in human RPE cells and enables its release in response to lipofuscin phototoxicity. Conclusion: C5a primes RPE cells for inflammasome activation by lipofuscin-mediated photooxidative damage. Significance: This mechanism provides a new link between key factors of AMD pathogenesis.

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Section: Discussioncontrasting

confidence: 81%

Complement Component C5a Primes Retinal Pigment Epithelial Cells for Inflammasome Activation by Lipofuscin-mediated Photooxidative Damage

Brandstetter

Holz

Krohne

2015

Journal of Biological Chemistry

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“…In the presence of increased oxidative stress, macrophages tend to adopt a more proinflammatory phenotype. 32 In addition, SP reduces oxidative stress in corneal wound healing. 33 In our mouse model, the skin proinflammatory condition at baseline in WT diabetic mice and in NK1RKO and TAC1KO mice was also associated with an elevated M1/M2 ratio.…”

Section: Discussionmentioning

confidence: 99%

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype

Leal

Carvalho

Tellechea

et al. 2015

The American Journal of Pathology

174

155

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Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. (Am J Pathol 2015 http://dx

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“…Furthermore, interactions between CEP and b 2 integrin could also trigger additional macrophage recruitment, stimulated by CEP-mediated outside-in signaling events. Taking into consideration the differential modulation of macrophage subtypes by CEP, as reported recently, 7,8 inflamed tissueexpressed CEP might turn out to play an important modulating role in fine-tuning the transition from the initial proinflammatory phase to the subsequent resolution phase of inflammation. …”

mentioning

confidence: 72%

“…Therefore, current research focuses on integrating clinical and biological markers to improve predictive power. 7 At present, many groups are generating high-dimensional data to describe the heterogeneous biology of follicular lymphoma. From the statistical learning perspective, data reduction is certainly needed to derive predictive models with acceptable generalizability to future patients.…”

mentioning

confidence: 99%

“…5 Furthermore, through interacting with TLR9 on platelets and TLR2 on macrophages, CEP was also identified as a prothrombotic and a proinflammatory factor, respectively. 6,7 In their article, Yakubenko et al report on the role of CEP in leukocyte trafficking during sterile inflammation. They showed in the inflamed peritoneal cavity of mice (after stimulation of the peritoneal cavity with thioglycollate over 72 hours) a strong upregulation of CEP expression compared with that in untreated tissue.…”

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confidence: 99%

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CEP: a new β2 integrin ligand in inflamed tissue

Sperandio

2018

Blood

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FLIPI was developed for overall survival and established in the prerituximab era. In contrast, FLIPI-2 was designed for progression-free survival, and, in its development cohort, more than one-half of patients had been treated with rituximabcontaining regimens. Notably, the PRIMA-PI represents a simplification of FLIPI-2, by using 2 of the 5 FLIPI-2 factors, although defining prognostic groups in a different way. From the point of view of statistical learning, predictive accuracy increases with higher model complexity, whereas the generalizability to future patients can be drastically reduced with high-dimensional data. 6 To what extent the reduction of FLIPI-2 factors is at the expense of lower predictive capacity remains to be determined. A fair comparison of PRIMA-PI and FLIPI-2 using the PRIMA cohort is not possible: PRIMA-PI is expected to be overfitted to its training cohort, whereas the evaluation of FLIPI-2 on the PRIMA cohort represents an independent validation (see figure). Unfortunately, the information on lymph node size necessary for the assessment of FLIPI-2 was missing in the validation cohort for PRIMA-PI. Thus, the head-to-head comparison of PRIMA-PI and FLIPI-2 represents an open question.The PRIMA-PI defines 3 prognostic groups with different clinical courses. Of note, the variability of outcome within the prognostic groups is still substantial. Therefore, current research focuses on integrating clinical and biological markers to improve predictive power.7 At present, many groups are generating high-dimensional data to describe the heterogeneous biology of follicular lymphoma. From the statistical learning perspective, data reduction is certainly needed to derive predictive models with acceptable generalizability to future patients. Whether a simplification of clinical data that are limited in number and have shown strong prognostic effects is a reasonable approach needs to be considered in future studies.The discrimination of outcome according to prognostic groups shown by Bachy et al indicates that current treatment, despite high efficacy, still needs improvement. Per current treatment guidelines, prognostic indices such as FLIPI, FLIPI-2, and PRIMA-PI should not be used to decide on specific therapies for a patient. Future studies on prognostic factors and, more importantly, on markers predictive of treatment response might give rise to novel individualized treatment strategies in patients with follicular lymphoma.

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The Oxidative Stress Product Carboxyethylpyrrole Potentiates TLR2/TLR1 Inflammatory Signaling in Macrophages

Cited by 27 publications

References 58 publications

Complement Component C5a Primes Retinal Pigment Epithelial Cells for Inflammasome Activation by Lipofuscin-mediated Photooxidative Damage

Complement Component C5a Primes Retinal Pigment Epithelial Cells for Inflammasome Activation by Lipofuscin-mediated Photooxidative Damage

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype

CEP: a new β2 integrin ligand in inflamed tissue

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