Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

Amorim, Natália; Souza-Almeida, Glaucia; Luna-Gomes, Tatiana; Bozza, Patrı́cia T.; Canetti, Cláudio; Diaz, Bruno L.; Maya‐Monteiro, Clarissa M.; Bandeira‐Melo, Christianne

doi:10.3389/fendo.2020.572113

Cited by 18 publications

(15 citation statements)

References 69 publications

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“…Leptin induces eosinophil activation, increasing the synthesis of lipid bodies and eicosanoids, such as LTC4, mediated by mTOR activation. Mast cells express LEPR and leptin signalling promotes the release of inflammatory mediators or cytokines, such as PGD2 and TNF-α, which are necessary for leptin-induced eosinophilic activation and migration [ 60 ].…”

Section: Physiology and Pathophysiology Of Leptinmentioning

confidence: 99%

An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage

Cordero-Barreal

González-Rodríguez

Ruiz-Fernández

et al. 2021

IJMS

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Since its discovery in 1994, leptin has been considered as an adipokine with pleiotropic effects. In this review, we summarize the actual information about the impact of this hormone on cartilage metabolism and pathology. Leptin signalling depends on the interaction with leptin receptor LEPR, being the long isoform of the receptor (LEPRb) the one with more efficient intracellular signalling. Chondrocytes express the long isoform of the leptin receptor and in these cells, leptin signalling, alone or in combination with other molecules, induces the expression of pro-inflammatory molecules and cartilage degenerative enzymes. Leptin has been shown to increase the proliferation and activation of immune cells, increasing the severity of immune degenerative cartilage diseases. Leptin expression in serum and synovial fluid are related to degenerative diseases such as osteoarthritis (OA), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Inhibition of leptin signalling showed to have protective effects in these diseases showing the key role of leptin in cartilage degeneration.

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Section: Physiology and Pathophysiology Of Leptinmentioning

confidence: 99%

An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage

Cordero-Barreal

González-Rodríguez

Ruiz-Fernández

et al. 2021

IJMS

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“…In mast cells, leptin also acts as a chemoattractant and provokes the generation of histamine, cysteinyl leukotrienes, CCL2 or ROS [ 52 ], as well as causing an eosinophilic inflammation through the activation of mast cell secretory activity mediated by TNF-a, CCL5 or PGD2 [ 53 ]. Moreover, leptin-deficient mast cells take part in anti-inflammatory processes [ 54 ].…”

Section: Role Of Leptin In Inflammationmentioning

confidence: 99%

Leptin, Both Bad and Good Actor in Cancer

Jiménez‐Cortegana¹,

López-Saavedra²,

Sánchez-Jiménez³

et al. 2021

Biomolecules

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Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. During the last decades, obesity and leptin have been associated with the initiation, proliferation and progression of many types of cancer. Obesity is also linked with complications and mortality, irrespective of the therapy used, affecting clinical outcomes. However, some evidence has suggested its beneficial role, called the “obesity paradox”, and the possible antitumoral role of leptin. Recent data regarding the immunotherapy of cancer have revealed that overweight leads to a more effective response and leptin may probably be involved in this beneficial process. Since leptin is a positive modulator of both the innate and the adaptive immune system, it may contribute to the increased immune response stimulated by immunotherapy in cancer patients and may be proposed as a good actor in cancer. Our purpose is to review this dual role of leptin in cancer, as well as trying to clarify the future perspectives of this adipokine, which further highlights its importance as a cornerstone of the immunometabolism in oncology.

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“…Knockout mice of Mmp9 , Cxcl1 , Ccl5 , Hdc and Stat1 are viable and may be obtained commercially from Jackson laboratory. Alternatively, neutralizing antibodies to Cxcl1 and Ccl5 can be used to block the function of the targets [ 43 , 44 ]. These studies likely generate additional ways to mitigate scleroderma development and progression.…”

Section: Discussionmentioning

confidence: 99%

A critical role of AREG for bleomycin-induced skin fibrosis

et al. 2021

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We report our discovery of an important player in the development of skin fibrosis, a hallmark of scleroderma. Scleroderma is a fibrotic disease, affecting 70,000 to 150,000 Americans. Fibrosis is a pathological wound healing process that produces an excessive extracellular matrix to interfere with normal organ function. Fibrosis contributes to nearly half of human mortality. Scleroderma has heterogeneous phenotypes, unpredictable outcomes, no validated biomarkers, and no effective treatment. Thus, strategies to slow down scleroderma progression represent an urgent medical need. While a pathological wound healing process like fibrosis leaves scars and weakens organ function, oral mucosa wound healing is a scarless process. After re-analyses of gene expression datasets from oral mucosa wound healing and skin fibrosis, we discovered that several pathways constitutively activated in skin fibrosis are transiently induced during oral mucosa wound healing process, particularly the amphiregulin (Areg) gene. Areg expression is upregulated ~ 10 folds 24hrs after oral mucosa wound but reduced to the basal level 3 days later. During bleomycin-induced skin fibrosis, a commonly used mouse model for skin fibrosis, Areg is up-regulated throughout the fibrogenesis and is associated with elevated cell proliferation in the dermis. To demonstrate the role of Areg for skin fibrosis, we used mice with Areg knockout, and found that Areg deficiency essentially prevents bleomycin-induced skin fibrosis. We further determined that bleomycin-induced cell proliferation in the dermis was not observed in the Areg null mice. Furthermore, we found that inhibiting MEK, a downstream signaling effector of Areg, by selumetinib also effectively blocked bleomycin-based skin fibrosis model. Based on these results, we concluded that the Areg-EGFR-MEK signaling axis is critical for skin fibrosis development. Blocking this signaling axis may be effective in treating scleroderma.

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Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

Cited by 18 publications

References 69 publications

An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage

An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage

Leptin, Both Bad and Good Actor in Cancer

A critical role of AREG for bleomycin-induced skin fibrosis

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